From the issue 23(1) we have implemented several major changes in the editorial policies and procedures. We hope that those changes will raise awareness of our potential authors and reviewers for research and publication integrity issues as well as to improve the quality of our submissions and published articles. Among those changes is the launch of a special journal section called Research Integrity Corner. In this section we aim to publish educational articles dealing with different research and publication misconduct issues. Moreover, we have done a comprehensive revision of our Instructions to authors. Whereas our former Instructions to authors have mostly been concerned with recommendations for manuscript preparation and submission, the revised document additionally describes the editorial procedure for all submitted articles and provides exact journal policies towards research integrity, authorship, copyright and conflict of interest. By putting these Guidelines into action, we hope that our main ethical policies and requirements are now visible and available to all our potential authors. We have also revised the former Authorship and copyright form which is now called the Author statement form. This form now contains statements on the authorship, originality of work, research ethics, patient privacy and confidentiality, and copyright transfer. Finally, Journal has adopted the ICMJE Form for Disclosure of Potential Conflicts of Interest. From this issue, for each submitted article, authors are requested to fill out the “ICMJE Form for Disclosure of Potential Conflicts of Interest” as well as the Author statement form and upload those forms during the online manuscript submission process. We honestly believe that our authors and readers will appreciate such endeavors. In this Editorial article we briefly explain the background and the nature of those recent major editorial changes.
scientific misconduct; plagiarism; editorial policies
Acute transverse myelitis is a rare clinical manifestation of Coxsackie virus infection which cause acute and progressive debilitating illness associated with loss of spinal cord function in the affected patients. A 62 year-old female developed symptoms of rapidly progressive paraplegia with sensory loss. On spinal MRI, T2 sagittal image showed increased signal intensity with cord swelling at T11-L2 level and 8 folds or greater rise of Coxsackie virus B4 neutralizing antibody titers was observed in the CSF. There is only one previous report of acute transverse myelitis caused by Coxsackie virus B4 infection to our knowledge. The presence of specific viral antibody titers change in the CSF and a corresponding spinal cord lesion are sufficient to suggest a causal relationship between the virus and the illness. This article is a case report of an unusual acute transverse myelitis caused by Coxsackie virus B4 infection.
Reovirus infection of the murine spinal cord (SC) was used as a model system to investigate innate immune responses during viral myelitis, including the activation of glia (microglia and astrocytes) and interferon (IFN) signaling and increased expression of inflammatory mediators. Reovirus myelitis was associated with the pronounced activation of SC glia, as evidenced by characteristic changes in cellular morphology and increased expression of astrocyte and microglia-specific proteins. Expression of inflammatory mediators known to be released by activated glia, including interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), chemokine (C-C motif) ligand 5 (CCL 5), chemokine (C-X-C motif) ligand 10 (CXCL10), and gamma interferon (IFN-γ), was also significantly upregulated in the SC of reovirus-infected animals compared to mock-infected controls. Reovirus infection of the mouse SC was also associated with increased expression of genes involved in IFN signaling, including IFN-stimulated genes (ISG). Further, reovirus infection of mice deficient in the expression of the IFN-α/β receptor (IFNAR−/−) resulted in accelerated mortality, demonstrating that IFN signaling is protective during reovirus myelitis. Experiments performed in ex vivo SC slice cultures (SCSC) confirmed that resident SC cells contribute to the production of at least some of these inflammatory mediators and ISG during reovirus infection. Microglia, but not astrocytes, were still activated, and glia-associated inflammatory mediators were still produced in reovirus-infected INFAR−/− mice, demonstrating that IFN signaling is not absolutely required for these neuroinflammatory responses. Our results suggest that activated glia and inflammatory mediators contribute to a local microenvironment that is deleterious to neuronal survival.
Trastuzumab is used as adjuvant treatment in patients with HER2-positive breast cancers and has been shown to reduce the chance of recurrence by up to 50%. However, experience with it given with radiotherapy is limited and there is in vitro evidence of a radiosensiti-sation effect. We describe the first case of trastuzumab-associated radiation-induced myelitis.
This patient received a calculated dose of 28 Gy to the spinal cord when receiving adjuvant radiotherapy to the chest wall and supraclavicular and axillary lymph nodes. This is well below the accepted radiation tolerance of the spinal cord (50-60 Gy) but she developed radiation-induced myelitis of her spinal cord with characteristic magnetic resonance imaging changes. We postulate that trastuzu-mab given concurrently with radiation may have acted as a radiosensitiser and that normal repair mechanisms in the acute stage were affected by trastuzumab blockage of epidermal growth factor receptors, resulting in demy-elination at a lower dose of radiation than normally seen.
Concomitant radiotherapy and adjuvant trastuzumab treatment should be given with caution and consideration made of delaying trastuzumab until after radiotherapy has been completed. As longer-term data become available for patients who received trastuzumab and radiation, it will become clearer whether there is a significant interaction on organs such as the heart and spinal cord in the radiation field.
Breast cancer; Chemotherapy; External beam radiotherapy; Trastuzumab; Radiosensitisation
Over the last 20 years, the number of publications outlining the advances in design strategies, growing techniques, and characterization of cocrystals has continued to increase significantly within the crystal engineering field. However, only within the last decade have cocrystals found their place in pharmaceuticals, primarily due to their ability to alter physicochemical properties without compromising the structural integrity of the active pharmaceutical ingredient (API) and thus, possibly, the bioactivity. This review article will highlight and discuss the advances made over the last 10 years pertaining to physical and chemical property improvements through pharmaceutical cocrystalline materials and, hopefully, draw closer the fields of crystal engineering and pharmaceutical sciences.
This review article will highlight and discuss the advances made over the last 10 years pertaining to physical and chemical property improvements through pharmaceutical cocrystals and, hopefully, draw closer the fields of crystal engineering and pharmaceutical sciences.
To evaluate the disinfection of dentinal tubules using calcium hydroxide with propylene glycol and calcium hydroxide with iodoform in silicone oil, as compared to 2% chlorhexidine gel.
Materials and Methods:
The antimicrobial efficacy of the medicaments against E.faecalis and C.albicans were assessed in vitro, using a dentinal tubule model at depths of 200 μm and 400 μm in extracted single rooted teeth. Saline was taken as the negative control (Group I)
All three medicaments used in this study exerted antibacterial and antifungal activity. Group II (calcium hydroxide with propylene glycol) and Group IV (2% chlorhexidine gel) had the highest antimicrobial activity and the differences between their antibacterial activities were not statistically significant. Group III (calcium hydroxide with iodoform in silicone oil) and Group IV had the highest antifungal activity and the differences between their antifungal activities were not statistically significant. The inhibition of growth at 200 μm and 400 μm was uniform, with no statistical difference.
Two percent chlorhexidine gel was effective against both E.faecalis and C.albicans. Calcium hydroxide with propylene glycol was the most effective intracanal medicament along with 2% chlorhexidine against E.faecalis, whereas, calcium hydroxide with iodoform in silicone oil was the most effective intracanal medicament along with 2% chlorhexidine against C.albicans.
C.albicans; chlorhexidine; E. faecalis; iodoform; propylene glycol; spectrophotometry
Critical care medicine frequently involves decisions and measures that may result in significant consequences for patients. In particular, mistakes may directly or indirectly derive from daily routine processes. In addition, consequences may result from the broader pharmaceutical and technological treatment options, which frequently involve multidimensional aspects. The increasing complexity of pharmaceutical and technological properties must be monitored and taken into account. Besides the presence of various disciplines involved, the provision of 24-hour care requires multiple handovers of significant information each day. Immediate expert action that is well coordinated is just as important as a professional handling of medicine's limitations.
Intensivists are increasingly facing professional quality management within the ICU (Intensive Care Unit). This article depicts a practical and effective approach to this complex topic and describes external evaluation of critical care according to peer reviewing processes, which have been successfully implemented in Germany and are likely to gain in significance.
peer review; quality management; intensive care medicine; evidence based medicine; effectiveness
A cost comparison study was made of Excerpta Medica's abstracting journals, based upon actual costs to a library. Unit costs were determined for six sections of EM as compared with six corresponding abstract journals. On average, EM sections were found to be 138% more costly than corresponding abstract journals. The effects of splitting of EM journal titles were also analyzed. This practice increases the price of a total subscription to EM and makes comprehensive information retrieval more difficult. A survey of medical school librarians as users of EM points to dissatisfaction with its increasing price, particularly when it results from title splitting.
Biochemia Medica has just established the Research integrity editor who will act as the Editorial team member responsible for all matters related to the various aspects of scientific misconduct. The major reason for this is the increasing number of various types of scientific misconduct in manuscripts submitted to our Journal. Research integrity editor will: a) strive to continuously raise awareness for research and publication integrity issues; b) educate our authors, reviewers and readers, by providing educational articles on various topics related to responsible research and writing; c) aim to prevent unethical research and publication practices; and d) responsibly deal with research and publication misconduct attempts in accordance with internationally accepted policies and recommendations. This initiative provides firm evidence of our commitment and respect for publishing ethical and responsible research. By this we hope to further increase the scientific quality of the journal content as well as the quality of the editorial work.
scientific misconduct; plagiarism; editorial policies
Engineered nanomaterials are at the leading edge of the rapidly developing nanosciences and are founding an important class of new materials with specific physicochemical properties different from bulk materials with the same compositions. The potential for nanomaterials is rapidly expanding with novel applications constantly being explored in different areas. The unique size-dependent properties of nanomaterials make them very attractive for pharmaceutical applications. Investigations of physical, chemical and biological properties of engineered nanomaterials have yielded valuable information. Cytotoxic effects of certain engineered nanomaterials towards malignant cells form the basis for one aspect of nanomedicine. It is inferred that size, three dimensional shape, hydrophobicity and electronic configurations make them an appealing subject in medicinal chemistry. Their unique structure coupled with immense scope for derivatization forms a base for exciting developments in therapeutics. This review article addresses the fate of absorption, distribution, metabolism and excretion (ADME) of engineered nanoparticles in vitro and in vivo. It updates the distinctive methodology used for studying the biopharmaceutics of nanoparticles. This review addresses the future potential and safety concerns and genotoxicity of nanoparticle formulations in general. It particularly emphasizes the effects of nanoparticles on metabolic enzymes as well as the parenteral or inhalation administration routes of nanoparticle formulations. This paper illustrates the potential of nanomedicine by discussing biopharmaceutics of fullerene derivatives and their suitability for diagnostic and therapeutic purposes. Future direction is discussed as well.
Metabolism; engineered nanomaterials; nanomedicine; fullerenol; carbon nanotube; titanium dioxide (TiO2); silica dioxide (SiO2); magnetic nanoparticles
The activity of most deoxyribonuclease enzymes can be monitored by measuring the change in absorbance at 260 nm which accompanies the breakdown of the double-stranded structure of native DNA. An automated method for determining deoxyribonuclease activity, based on such an absorbance change, which can overcome problems of inhibition arising from the presence of inorganic cations, is described. Variations in inorganic cation concentration is a particular problem when measuring the activity of chromatographic fractions eluted via a salt gradient. A comparison is made between the automated and a manual method for the assay of deoxyribonuclease active constituents, of the medicament ‘Varidase’, eluted from a Cellex-D (Bio-Rad Laboratories Ltd) anionic exchange resin using a 0.05-1.0 M sodium chloride gradient.
Panchakarma is the most essential part of Ayurveda treatments. It is preventive, preservative, promotive, curative and rehabilitative therapy. Ayurveda believes in strong relationship between macrocosm and microcosm and states that the seasonal changes will influence the biological systems resulting into the accumulation and aggravation of particular Dosha in a particular season like accumulation and aggravation of Kapha in Hemant Rutu (winter season) and Vasant Rutu (spring season) respectively, accumulation and aggravation of Pitta in Varsha Rutu (rainy season) and Sharad Rutu (autumn season) respectively. Vasantika Vamana is done in spring season approximately in the month of March and April for the elimination of vitiated Kapha Dosha which in turn helps to prevent the forth coming Kapha disorders and associated Pitta disorders or diseases originating or settled in the place of Kapha like bronchial asthma, allergic bronchitis, rhinitis, sinusitis, migraine, hyperacidity, indigestion, anorexia, obesity, overweight, dyslipidemia, diabetes mellitus, acne vulgaris, psoriasis, eczema, urticaria etc. In this study, a total of 89 persons were registered and 69 volnteers/patients undergone classical Vamana Karma without any major complications. Average minimum, maximum, total dose and total days of Snehapana were 36.40 ml, 187.21 ml, 578.59 ml and 5.01 days respectively. Average quantity of Madanaphala, Ksheera, Yashtimadhu Phanta and Lavanodaka was 5.81 g, 1130.29 ml, 3202.9 and 2489.13 ml respectively. The results were encouraging; hence, further studies may be conducted including large population in this direction.
Antiki; Dosha; Kapha; Laingiki; Madanaphala; Maniki; Pitta; Samsarjana Krama; Snehapana; Vasantika Vamana; Vegiki
Sarvanga Swedana is a common procedure done in Ayurvedic Panchakarma units. Passive body heat therapy, which is akin to Sarvanga Swedana is known to cause systemic hemodynamic changes. Such studies would have been required to find the possible hemodynamic changes following the Sarvanga Swedana sessions also. An observational study was planned to observe hemodynamic changes among patients routinely receiving Sarvanga Swedana in a Panchakarma setting at an Ayurvedic hospital. Significant increase in blood pressure and pulse rate (PR) was observed in all patients immediately after the completion of Sarvanga Swedana therapy. Upon continuation of Sarvanga Swedana in a subgroup; however, a significant reduction in systolic blood pressure and PR was also observed.
Blood pressure; hemodynamic changes; Panchakarma; Swedana
Globally the medical device (MD) market has been growing quite rapidly over the past decade. The regulatory framework for pharmaceuticals and devices differ substantially. The regulatory authorities in different regions of the world recognize different classes of medical devices (MDs), based on their design complexity, their use characteristics, and their potential for harm, if misused. With the vast majority of MDs in developing countries being imported, the respective governments need to put in place policies & regulations to address all elements related to MDs, ranging from its development, manufacturing, registration to post-marketing obligations & disposal so that public can have access to high quality, safe & affordable products for appropriate use. This article highlights current regulations pertaining to registration of MDs in India, in light of those existing in Global Harmonization Task Force (GHTF) member countries & Association of Southeast Asian Nations (ASEAN) countries.
Medical device; Regulations; Registration
To describe clinical, MRI and cerebrospinal fluid (CSF) features of a varicella zoster virus (VZV) related meningo-encephalo-myelitis (MEM) without rash in an immunocompetent female.
An 85 year old immunocompetent woman with mild hyperthermia and acute, severe MEM.
Serum antibodies and CSF PCR were searched for several viruses. Brain and spinal cord MRI were performed. Immunological profile.
i.v. acyclovir 30 mg/kg/day; i.v. 6-MP 125 mg/day.
Marked CSF lymphomonocytic pleocytosis, blood-brain-barrier damage, and PCR detection of 3.05 X 10 6 copies of VZV DNA. MRI revealed lesions of the meninges, brain and spinal cord. No evidence of immunosuppression.
We highlight the importance of considering the possibility of VZV related MEM, even in immunocompetent patients. We also provide a MRI description of VZV related multifocal myelitis, not previously available. As supported by other reports, we underline the necessity of a prompt therapeutic intervention in this life-threatening condition
varicella-zoster; meningitis; encephalomyelitis; immunocompetence; vasculitis
Psychiatric morbidity may be highly prevalent in transverse myelitis (TM), but data on this aspect are limited.
To assess psychiatric morbidity in a clinical sample of patients with idiopathic TM compared to patients with a recent stroke.
Materials and Methods:
Consecutive patients with idiopathic TM and stroke (30 each) underwent two-stage screening with the General Health Questionnaire-12 (GHQ-12) and Structured Clinical Interview for Axis I DSM-IV Disorders – Clinician Version (SCID I-CV), and ratings of depression, disability levels, and cognitive impairment.
Seventy percent of the patients with TM scored above the cut-off on the GHQ; 30% had a positive diagnosis of a psychiatric disorder. Major depression (17%) was the commonest psychiatric disorder. Mini-Mental State Examination (MMSE) scores indicated cognitive impairment in 23% of patients with TM. Higher GHQ-12 scores were associated with greater disability. These results were similar to those obtained among patients with stroke.
A high prevalence of psychological distress and psychiatric morbidity was found in idiopathic TM. This morbidity was associated with greater disability.
Psychiatric morbidity; stroke; transverse myelitis
Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system (CNS), respectively. Indeed, the number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal CNS infections, on the other hand, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with non-infectious disorders that cause acute flaccid paralysis (AFP). This chapter will review some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus will be placed on the diseases caused by enteroviruses (EVs), which as a group account for the vast majority of all aseptic meningitis cases as well as many focal infections of the spinal cord.
aseptic meningitis; myelitis; acute flaccid paralysis; enterovirus; cerebrospinal fluid; neurovirology
The anti-aquaporin4 (anti-AQP4) antibody is specific for neuromyelitis optica (NMO), but is also found in limited forms. The presence of this antibody in acute transverse myelitis (ATM) has been associated with recurrence and conversion to NMO, but the influence on disability has not yet been described.
To describe the frequency of anti-AQP4 in ATM and analyze the influence in long-term prognosis.
Cross-sectional and retrospective study.
Consecutive ATM cases in a multiple sclerosis center in Rio de Janeiro, Brazil, from 2000 through 2009 were reviewed. Recurrent cases tested for anti-AQP4 were selected. ATM with magnetic resonance imaging spinal cord lesions extending over three or more vertebral segments was classified as longitudinally extensive transverse myelitis (LETM); Kurtzke scale was applied at last evaluation.
Frequency of anti-AQP4; severity of spinal cord dysfunction at last follow-up.
Twenty six patients (21 female:5 male; 17 white:9 African descent) were studied. The first ATM occurred at 38.04 ± 12.7 years. The interval between the first and the second ATM was eight months (1–150) and the number of ATM varied from two to seven. After 40.5 months (12–192) of disease, the median Expanded Disability Status Scale (EDSS) score was three (0–9). Anti-AQP4 antibody was positive in 26.9%. LETM was found in 65.4%. LETM presented later onset, higher disability and higher positivity to anti-AQP4 (LETM 41.2% versus no-LETM 0%, P = 0.024). Dysfunction at long-term follow-up was similar in anti-AQP4 positive and negative cases.
The frequency of anti-AQP4 in recurrent ATM was 26.9%, increasing to 41.2% among LETM. Presence of the antibody had no influence on morbidity.
Transverse myelitis; Demyelinating diseases; Neuromyelitis optica; Anti-AQP4 antibody; Disability; Multiple sclerosis; Disability; Paresis
Eosinophilic myelitis (EM) or atopic myelitis is a rare disease characterized by a myelitic condition in the spinal cord combined with allergic process. This disease has specific features of elevated serum IgE level, active reaction to mite specific antigen and stepwise progression of mostly the sensory symptoms. Toxocariasis can be related with a form of EM. This report describes two cases of cervical eosinophilic myelitis initially considered as intramedullary tumors. When a differential diagnosis of the intramedullary spinal cord lesion is in doubt, evaluation for eosinophilic myelitis and toxocariasis would be beneficial.
Allergy; Eosinophilic myelitis; Intramedullary tumor; Toxocariasis
Transverse myelitis (TM) is an inflammatory process involving a restricted area of the spinal cord. The usual dramatic presentation makes TM a medical emergency. Early detection and aggressive therapy are required in order to improve the prognosis. The association of this unique clinical phenotype and autoantibody provides circumstantial evidence that an autoimmune aetiology might be involved. We describe two cases of TM associated with anti-Ro (SSA) autoantibodies without connective tissue disease manifestations. The two patients were treated successfully with IV steroids and cyclophosphamide.
Vogt-Koyanagi-Harada (VKH) disease is characterized by bilateral granulomatous uveitis with neurologic, auditory, and dermatologic manifestations. However, acute myelitis complicating VKH disease has rarely been reported.
A 50-year-old Chinese Han woman presented with difficulty walking, numbness on the left side of the body, and difficulty with urination. The patient was diagnosed with incomplete VKH disease and received corticosteroid treatment prior to the neurological presentation. Acute myelitis was diagnosed based on both clinical and spinal-cord MRI findings.
Clinicians should consider acute myelitis as a rare possible neurological manifestation in VKH disease patients, and early systemic administration of corticosteroids will suppress the acute inflammatory process and prevent recurrences. This report raises the possibility that VKH disease and acute myelitis share common pathogenic pathways.
Vogt-Koyanagi-Harada disease; acute myelitis; pathogenesis
In Charak Samhita, all the treatment modalities have been classified broadly into six types, i.e., Langhana (depleting therapy), Brimhana (nourishing therapy), Rookshana (dehydrating therapy), Snehana (oleation therapy), Swedana (sudation therapy) and Stambhana (astringent therapy). Out of these six types, Rookshana is of the same importance as others but is used less frequently as main line of treatment. Since decades, Ayurveda treatment is considered most promising treatment for neurological disorders. Most of the neurological disorders are generally considered to be Vata Vyadhis in which Snehana Karma is recommended. In case of neurological disorders if symptoms are suggestive of Kapha dominance, then Rookshana must be done initially. Transverse myelitis is a neurological disease, which has an autoimmune process involved in its pathology. It is an acute, subacute, generally monophasic inflammatory disease of the spinal cord. In the present case of transverse myelitis, the patient was found having Kapha dominant symptoms such as coldness of feet, loss of appetite etc., and so the patient was subjected to Rookshana Karma in various forms. Just after 15 days, all these symptoms were subsided and tremendous improvement was found thereafter. The paraplegic patient under study was able to walk independently in just two and half months of treatment. All other typical features related to the disease were also improved. This particular case has proved the importance of Rookshana therapy in neurological disorders.
Ayurveda; Rookshana Karma; transverse myelitis; Urustambha
Recurrent zoster myelitis is quite rare. We present a previously healthy 27-year-old woman who developed recurrent attacks of myelopathy shortly after the characteristic skin rashes of herpes zoster. Magnetic resonance imaging studies demonstrated each lesion in the spinal cord at the same segments as the skin lesions. She had two attacks at opposite sites at the same spinal cord level and complete recovery after being treated with intravenous acyclovir. We suspect that direct invasion of varicella zoster virus was the cause of recurrent myelopathy in our patient.
The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity.
Radiation myelitis is the most serious complication in clinical radiotherapy for spinal metastases. We previously showed that 125I brachytherapy induced apoptosis of spinal cord neurons accompanied by autophagy. In this study, we further investigated the mechanism by which 125I radiation triggered autophagy in neural cells. We found that autophagy induced by 125I radiation was involved in endoplasmic reticulum (ER) stress and mainly dependent on PERK-eIF2α pathway. The expressions of LC3II, ATG12 and PI3K were significantly suppressed in PERK knockout neural cells. Meanwhile, the expressions of phosphorylated-Akt s473 and caspase3/8 all significantly increased in neural cells transfected with a PERK siRNA and which enhanced apoptosis of neurons after 125I radiation. The results were consistent with that by MTT and Annexin-FITC/PT staining. In annimal model of banna pigs with radiation myelitis caused by 125I brachytherapy, we have successfully decreased PERK expression by intrathecal administration of the lentivirus vector. The apoptosis rate was significantly higher than that in control group and which deteriorated radiation myelitis of banna pigs. Thus, autophagy caused by 125I radiation was mainly as an attempt of cell survival at an early stage, but it would be a self-destructive process and promoted the process of apoptosis and necrosis radiated by 125I for more than 72 hours. The study would be useful and helpful to maximize efficiency of radiation therapy in clinical therapy.