Chronic Ones Research Articles

Multimodal sensing and therapeutic systems for wound healing and management: A review

Wounds especially chronic ones significantly affect the quality of patients’ life and present a severe financial burden for the healthcare industry. Timely and effective management of wounds, such as diagnosing wound parameters, treating various wound symptoms, and reducing infection at the wound noninvasively, is very important for accelerating wound healing and relieving patients’ pain. Recent years have seen significant efforts dedicated to developing technologies for monitoring various biomarkers vital to the wound healing process including temperature, pressure, pH, and the infection status to assist with the diagnosis and treatment of wounds, as well as advanced wound therapies such as on-demand and local drug delivery. This review paper introduces recent progress on multimodal sensing and therapeutic systems for wound healing. Specifically, we focus on physical sensing (temperature, moisture, pressure, and strain), chemical sensing (pH, uric acid, and cytokine), as well as therapeutic systems for wound management (active drug delivery systems based on external stimulations and non-drug stimulations). In addition, leveraging advanced analytic techniques, i.e., machine learning and deep learning, for data-driven assessment and management of the wound healing process has been discussed.

Framework for real-time monitoring E-Health systems

Health information is important for monitoring and improving people's health. The results of the study prove that in Kosovo the health system still has problems in providing health services, in both professional and technical aspects. This is due to the lack of a unique electronic health system that would monitor patients' health status and possess important information about them, especially acute and chronic ones. Lack of health information also affects the quality of health services provided. Improvement of the health system in Kosovo is achieved when the information system addresses national demands and problems. The progress of healthcare delivery relies on good decision-making in the implementation of the long-term strategy involving all stakeholders in the health system. Best practices, challenges and lessons learned in health system implementation in developed countries are guidelines for developing information systems in developing countries, such as Kosovo, This paper has been carried out by incorporating data imbibed at scientific level as well paying visits and making interviews with the respective interested parties. As a result of the acquired data and feedback, there has been concluded that there in an urging need to undertake tremendous investments to improve the contact with patients thrugh the ICT..

Wearable Sensors for the Detection of Biomarkers for Wound Infection.

Infection represents a major complication that can affect wound healing in any type of wound, especially in chronic ones. There are currently certain limitations to the methods that are used for establishing a clinical diagnosis of wound infection. Thus, new, rapid and easy-to-use strategies for wound infection diagnosis need to be developed. To this aim, wearable sensors for infection diagnosis have been recently developed. These sensors are incorporated into the wound dressings that are used to treat and protect the wound, and are able to detect certain biomarkers that can be correlated with the presence of wound infection. Among these biomarkers, the most commonly used ones are pH and uric acid, but a plethora of others (lactic acid, oxygenation, inflammatory mediators, bacteria metabolites or bacteria) have also been detected using wearable sensors. In this work, an overview of the main types of wearable sensors for wound infection detection will be provided. These sensors will be divided into electrochemical, colorimetric and fluorimetric sensors and the examples will be presented and discussed comparatively.

Fixed nature and dynamic processes in Hahnemann's thought

Background and Aims. At least since classical Greek philosophy two opposite vews are facing, the one of Heraclitus, affirming that all things are in a continuous flux, and the other of Parmenides, the assertor of changelessness. The aim of present contribution is to consider if and how the tension between such views continues to permeate several features of the culture, including the thought of S. Hahnemann.
 Methods. This will be achieved through the examination of some cases in the natural sciences and human sciences, including Hahnemann’s writings.
 Few examples are presented here. The living being can be viewed as a thing genetically determined, or as an open and dynamic complex of processes interacting mutually and with the environment at metabolic and informational levels. The central nervous system is seen to underlie both automatic, and creative behaviours. A species is considered a pure ideal type, or a historically varying population of similar individuals. The basic traits of human behaviour are attributed to an unchanging nature (better, a nature undergoing slow Darwinian changes), or to a culture evolving in a rapid Lamarckian way. Within an integrated view of the person one may consider both the four fixed human constitutions (see H. Bernard; M. Martiny; N. Pende; A. Negro), and their four changing constitutional stages (see H. Bernard). Classical culture highlights the paramount importance of universal principles, while postmodern culture highlights proteanism, liquid state, patchwork.
 In particular, we may encounter such two views in the thought of Hahnemann on diseases. They are found in his writings respectively on the chronic diseaes, and on the so-called non-miasmatic diseases. About chronic diseases, he wrote that they are primitive, deeply-rooted, underlying external symptoms, old, universal, always recurring, internal, and do not desappear even when external symptoms of acute diseases desappeared, while the whole symptoms of them must be extensivery taken into account. About non-miasmatic diseases, he wrote that the complex of symptoms of a single case, which is always different for each individual case, cannot be foreseen, nor schematized, nor taken as a model, nor treated by an a priori chosen remedy or with a priori rules different from the strict application of the so-called law of similars, experimentally established.
 Conclusions. We may conclude that Hahnemann’s integrated consideration of diseases takes into account both the fixed characteristics of the chronic ones and the dynamic processes of the acute ones, so that the two above views appear to be not opposed, but perfectly integrated.

The complexity of social work at hospitals during the pandemic in Germany

Social work is also an indispensable pillar in the healthcare of patients in hospitals (Homfeldt, 2012, p. 489). Hospital social services support patients in processing stressful diagnoses and coping with the consequences of diseases (Gödecker-Geenen, 2005, p. 19). Due to the current development of problem situations and the current structure of health and social care, social work is gaining more and more importance (Schaub, 2008, p. 17; Hofmann, 2004, p. 413). Demographic changes result in an increase in the number of elderly people and a steady increase in their life expectancy. The lack of family or financial resources creates gaps in the supply of hospital social services (Meyer, 2019, p. 9). However, the change in the spectrum of health risks and diseases from predominantly acute to chronic ones, justifies the importance of social work in these facilities (Schaub, 2008, p. 17; Lützenkirchen, 2005, pp. 10–14). The Covid-19 pandemic presents a particular challenge that has spread around the world since late 2019. It affects all areas of life and life situations (Schmitt, 2020, p. 177). Protective measures to contain the virus, such as mass gathering prohibitions, contact restrictions, minimum distance regulations, hygiene measures and masks, determine daily and social life. Preventing visits from relatives, pastors and social workers puts a new light on the holistic view of health and the disease and its social determinants (Kröll et al., 2020, pp. 7–38). Infection protection legislation also restricts community services from interacting with patients and hospital staff. Work processes and communication must change, and existing systems must be redesigned (Truell, 2020).

Analysis of the Structure of Contractures of the Upper Limb Joints

Summary. Analysis of the restrictions in the amplitude of movements in the joints is traditionally considered from the standpoint of individual nosologies that cause them, but the systemic results of the inverse syndromological approach to the study of contractures are published only sporadically.
 Objective: to determine the structure, causes, nature, and severity of contractures of the upper extremity joints.
 Materials and Methods. The structure of contractures of the upper extremity joints as the consequences of injuries and diseases was analyzed on a large array of patients (16,710 patients). Distribution by location, etiology, severity of contracture, gender and age, and relationships between type and localization of contracture were assessed. The dynamics of the development of contractures and the number of necessary surgical interventions was traced.
 Results. Restriction of movements in the upper extremity joints was registered in 5,450 out of 16,710 (32.6%) patients; among them there were 3,485 male (63.9%) and 1,965 (36.1%) female patients. During reconstructive treatment, 7,892 surgeries were performed. Most often these were contractures of the finger joints (42.5%), then shoulder (26.9%), elbow (13.4%), carpal joint (13.3%), less often – radioulnar contractures (3.9%). The elbow, radioulnar and carpal joint contractures most often are caused by osteo-cartilaginous lesions; a polyetiological component is typical for the finger joints. The shoulder joint contractures may be caused evenly by desmogenic, myogenic, or osteo-cartilaginous lesions. Most of the joint contractures are of moderate severity. Contractures of the fingers require multi-stage surgical treatment (1.91±1.35 surgeries); one-stage treatment is used for contractures of the shoulder joint (1.34±0.81 surgeries). The most polystructural lesions were combat wounds, ischemic, and finger contractures (2.53±1.22; 2.52±1.34 and 2.5±1.24 structures, respectively), and the least – radioulnar contractures (1.59±1.34 structures). Radioulnar contractures in 37.3% of cases are accompanied by contractures of the fingers, but vice versa only in 1.2%. It was noted that contractures of the radioulnar joints are often accompanied by restriction of movements in the elbow and wrist joints – in 34.9 and 56.6% of cases, respectively. At the same time, the inverse dependence of the combination of contractures in the wrist and elbow joints with radioulnar joints is not very high – 4.2% and 6% of cases, respectively.
 Conclusions. In patients who are hospitalized for highly specialized surgical treatment of pathology of the upper extremity, contractures of its joints are moderate and severe, characterized by polyetiology, and, in most cases, caused by disorders of osteo-cartilaginous structures and their combination with desmogenic, tenogenic, and myogenic lesions. Specific relationships are traced in localization and mutual burden of contractures, rapidity of their progression. As a rule, upper limb contractures are chronic ones and require multi-stage surgical treatment.

Alkyl-Quinolones derivatives as potential biomarkers for Pseudomonas aeruginosa infection chronicity in Cystic Fibrosis

In Cystic Fibrosis (CF), a rapid and standardized definition of chronic infection would allow a better management of Pseudomonas aeruginosa (Pa) infections, as well as a quick grouping of patients during clinical trials allowing better comparisons between studies. With this purpose, we compared the metabolic profiles of 44 in vitro cultures of Pa strains isolated from CF patients at different stages of infection in order to identify metabolites differentially synthetized according to these clinical stages. Compounds produced and secreted by each strain in the supernatant of a liquid culture were analysed by metabolomic approaches (UHPLC-DAD-ESI/QTOF, UV and UPLC-Orbitrap, MS). Multivariate analyses showed that first colonization strains could be differentiated from chronic colonization ones, by producing notably more Alkyl-Quinolones (AQs) derivatives. Especially, five AQs were discriminant: HQC5, HQNOC7, HQNOC7:1, db-PQS C9 and HQNOC9:1. However, the production of HHQ was equivalent between strain types. The HHQ/HQNOC9:1 ratio was then found to be significantly different between chronic and primo-colonising strains by using both UV (p = 0.003) and HRMS data (p = 1.5 × 10–5). Our study suggests that some AQ derivatives can be used as biomarkers for an improved management of CF patients as well as a better definition of the clinical stages of Pa infection.

Saudi Honey: A Promising Therapeutic Agent for Treating Wound Infections.

Treatment of wounds, especially chronic ones, is a major challenge in healthcare, with serious clinical and economic burdens. Multiple treatment approaches, including the usage of silver and iodine, have dramatically improved wound healing and reduced the incidence of infection. However, once infected by drug-resistant bacteria, treatment of wounds becomes a serious complication, with limited availability of effective antibiotic drugs, leading to high morbidity and mortality. Therefore, alternative therapeutic agents are required to address this gap in wound management. The introduction of manuka honey as a therapeutic agent against infected wounds was the result of extensive research about its activity against both planktonic and biofilm bacterial growth. Likewise, several types of Saudi honey (e.g., Sidr and Talh) showed promising in vitro and in vivo antimicrobial activity against wound pathogens. This short review summarizes literature that investigated the activity of common types of Saudi honey in relation to wound infections and explores their clinical utility.

Efficacy of homoeopathy in management of migraine

Migraine is a neurological painful condition that affects millions of people. It is the most common neurological disease that has a significant effect on the brain and behaviours associated with repeated migraine attacks. Chronic migraine is a condition in which a patient experiences a one-sided throbbing headache for at least 15 days in a month. Patients with chronic migraine present in primary care are often referred for management to secondary care, hence, increasing the number of patients in the clinic. The conclusion drawn from this article is how homoeopathy has the potential to manage migraine headaches especially chronic ones and give permanent and effective results to the affected patients.

Портальная гипертензивная гастропатия (Обзор литературы)

Статья посвящена портальной гипертензивной гастропатии (ПГГ) — вторичному изменению слизистой оболочки и подслизистого слоя желудка на фоне цирроза печени (ЦП) любой этиологии и сопутствующей ему портальной гипертензии. В обзоре представлены данные, касающиеся истории изучения данной патологии, эпидемиологии, патогенеза, клинических проявлений, методов диагностики и лечения. Показано, что в основе заболевания лежит портальная гипертензия, приводящая к нарушению микроциркуляции в слизистой желудка, и как следствие — к полнокровию и венозному застою. Клиническое течение ПГГ в большинстве случаев бессимптомное. Основным методом диагностики является эндоскопический, базирующийся на определенных макроскопических признаках. В обзоре рассмотрены основные эндоскопические классификации ПГГ. Основные гистологические изменения при ПГГ включают расширение капилляров и венул в слизистом и подслизистом слое без существенного воспаления. Течение ПГГ динамичное. К осложнениям ПГГ относятся хронические и, реже, острые кровотечения. Лечение медикаментозное, с использованием неселективных бета-блокаторов

Морфологічні зміни головного мозку при діабетичній енцефалопатії

Метою наведеної роботи було вивчення морфологічних характеристик змін головного мозку у хворих із діабетичною енцефалопатією (ДЕ) на підставі дослідження аутопсійного матеріалу. Матеріали та методи. В роботі наведено результати 14 секційних спостережень. Середній вік хворих становив 51,0 ± 3,4 року. Шматочки мозку фіксували в розчині IHC Zink Fixative, виготовляли серійні парафінові зрізи товщиною 10 ± 1 мкм. Препарати фарбували гематоксиліном і еозином, конго рот, тіоніном за методом Ніссля, ставили ШИК-реакцію, імпрегнували нітратом срібла за методом Більшовського і хлоридом золота за Кахалем, проводили морфометричне дослідження за Г.Г. Автанділовим. Препарати досліджували на мікроскопі Olympus AX70 з цифровою камерою Olympus DP50. Мікрофотографування препаратів здійснювалося з використанням програми AnalysisPro 3.2. Результати. Основними цито-ангіоархітектонічними проявами ДЕ є дифузна альтерація базальних мембран і ендотелію судин мікроциркуляторного русла, меншою мірою — артеріол, внутрішньомозкових артерій і вен. Висока щільність (питомий обсяг) капілярної мережі при ДЕ морфологічно відображає картину капілярного паралітичного застою. Капілярний застій супроводжується стазом крові, збільшенням навколосудинного капілярного простору (простір Вірхова — Робіна), ширина якого є морфологічним еквівалентом лімфатичної дисциркуляції. Ранні морфологічні ушкодження стінок капілярів — потовщення і розщеплення основної мембрани з накопиченням ШИК-позитивних речовин, вогнищева проліферація ендотеліоцитів. До пізніх пошкоджень відносяться капілярний фіброз і гіаліноз, проліферація перицитів, що супроводжується різким порушенням транскапілярного транспорту. Порушення стріарної і радіарної цитоархітектоніки в I–IV шарах головного мозку, випадіння нейронів (нейрональні спустошення) проявляються вогнищевим випадінням гангліозних і пірамідальних клітин. Висновки. Ранніми зворотними морфологічними змінами нейронів є набухання нейронів (гідропічна дистрофія нервових клітин), вогнищевий гіперхроматоз. Незворотними структурними ушкодженнями нейронів є лізис ядра і ядерця з гомогенізацією цитоплазми, формування клітин-тіней, вакуолізація цитоплазми, перицелюлярний набряк, лізис відрост­ків у поєднанні з нейрофагією. Є характерним поєднання гострих альтернативних ушкоджень нейронів із хронічними (ішемічного характеру) — пікноз, зморщування ядер з вираженою атрофією цитоплазми.

A qualitative approach to identify barriers to multi-professional teamwork among medical professors at Iranian teaching hospitals

BackgroundIn some cases of diseases, such as infectious, neurological and chronic ones prevention and treatment is complex. Therefore, a single medical specialty alone cannot effectively manage treatment of patients due to health care needs of them and complexities of treatment. Instead, a team composed of different healthcare disciplines with effective, continuous, and organized communication must follow up various aspects of patient care. In this regard, the present qualitative study aimed to shed light on the experiences of clinical teachers of multi-professional teamwork barriers within Iranian teaching hospitals.MethodsIn this qualitative research, the experiences of medical clinical teachers of multi-professional teamwork barriers within teaching hospitals were explained. Sampling was theoretical and the data were collected from experienced clinical teachers and medical students studying at several Universities of Medical Sciences through semi-structured interviews and observation, which were continued until data saturation. Fifteen clinical teachers and five medical students participated in the study. The interviews were analyzed using conventional content analysis.ResultsThree main categories were extracted. The first category was “enhancing the culture of interdisciplinary education” included “paving the way for an interdisciplinary culture”, “enhancing teamwork culture”, and “having a general view of medical sciences instead of specialization”. The second category was “barriers of interdisciplinary education” included “influence of the dominant culture of specialization in society”, “poor interdisciplinary education infrastructure”, and “individualism as a value of society”. And the third category was “consequences of specialization” included “medical sciences education under the shadow of specialization”, “possibility to harming patients”, and “distrust of society in the services provided by the 1st and 2nd level centers”.ConclusionIt seems that attitudinal barriers, teamwork difficulties, and the culture of individualism are evident in Iran; more, roles of the healthcare team and the status of each member is not clear. Designing interactive curriculum and arranging clinical settings to facilitate exchange of ideas among clinical teachers and students of different disciplines, is a step forward to achieving a common value concept, language, and common perception, and establishing cooperation and understanding among disciplines involved, which leads to further understanding of the professional responsibilities of other disciplines.

Factors associated with post-infarction myocardial remodeling

This article analyzes the problem of postinfarction myocardial remodeling in the current availability of high-tech methods of coronary revascularization in most countries. The authors discuss both wellstudied factors that determine the transformation of acute myocardial injury into chronic heart failure syndrome and new fundamental ones that determine prognosis and treatment. Used information on the topic from publications over the past five years, based on the PubMed, Google Scholar and Russian Science Citation Index databases.

Bioluminescent Imaging Identifies Thymus, As Overlooked Colonized Organ, in a Chronic Model of Leishmania donovani Mouse Visceral Leishmaniasis.

The search for new drugs against neglected parasitic diseases has experienced a major boost in recent years with the incorporation of bioimaging techniques. Visceral leishmaniasis, the second more neglected disease in the world, has effective treatments but with several disadvantages that make the search for new therapeutic solutions an urgent task. Animal models of visceral leishmaniasis that resemble the human disease have the disadvantage of using hamsters, which are an outbred breeding animal too large to obtain acceptable images with current bioimaging methodologies. Mouse models of visceral leishmaniasis seem, however, to be more suitable for early (acute) stages of the disease, but not for chronic ones. In our work, we describe a chronic Balb/c mouse model in which the infection primarily colonizes the spleen and well recreates the late stages of human disease. Thanks to the bioluminescent image, we have been able to identify experimentally, for the first time, a new primary lymphoid organ of colonization, the thymus, which appears infected from the beginning until the late phases of the infection.

Three-dimensional ultrashort echo time (3D UTE) magnetic resonance imaging (MRI) of the normal and degenerative disco-vertebral complex at 4.7T: a feasibility study with longitudinal evaluation.

To assess feasibility of a three-dimensional ultrashort echo time (3D-UTE)-sequence to evaluate normal and pathological disco-vertebral complex (DVC), with assessment of its different portionsin a rat model of degenerative disk disease (DDD) with histological correlation.To assess whether this sequence, in comparison with long echo time T2-weighted sequence, is able to monitor DDD with differentiation of early from chronic DVC changes in pathological mechanical conditions. Five rats were induced with DDD model by percutaneous disk trituration of the tail with an 18-G needle under US-guidance and imaged at 4.7T. MRI protocol included fat-saturated-T2 (RARE) and 3D-UTE-sequences performed at baseline (day 0. n = 5 animals /10 DVC) and each week (W) from W1 to W10 postoperatively. Visual analysis and signal intensity measurements of SNR and CNR of all DVC portions were performed on RARE and UTE images. Following killing (baseline, n = 1/2 DVC; W2, n = 2/4 DVC; W10, n = 2/4 DVC), histological analysiswas performed and compared with MRI. In normal DVC, unlike conventionalRARE-sequences, 3D-UTEallowed complete identification of DVC zonal anatomy including on visual analysis and CNRmeasurements. In pathological conditions, SNR and CNR measurements of the annulus fibrosus and nucleus pulposus on 3D-UTE distinguished early discitis at W1 fromchronic discopathy (P < 0.001 for SNR and P < 0.001 for CNR). Neither the normal complete anatomy of the DVC nor its pathological patterns could be assessed on conventional sequences. Unlike conventional sequences, 3D-UTE enables visualization of the complete normal DVC anatomy and enables monitoring of DDD differentiating between earlyDVC changes from chronic ones. Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Pediatric immune thrombocytopenia: apoptotic markers may help in predicting the disease course.

In all, 15-30% of pediatric immune thrombocytopenia (ITP) patients will remain chronically thrombocytopenic at 1 year post diagnosis. All attempts to classify patients at diagnosis have proven unsuccessful. We hypothesized that a different pathophysiology is responsible for non-chronic versus chronic pediatric ITP. We aimed to examine differences in the apoptotic markers' presentation at diagnosis between non-chronic and chronic patients. Blood samples were collected from 42 pediatric patients with newly diagnosed ITP prior to initiation of treatment. We incubated patients' sera with control platelets and compared the results among three research groups: healthy controls, chronic ITP, and non-chronic ITP patients. We measured apoptotic markers phosphatidylserine (PS) exposure and mitochondrial inner membrane potential (ΔΨm) by flow cytometry and the level of human apoptotic proteins by Human Apoptosis Array. We found increased platelet PS exposure and decreased ΔΨm in response to all ITP patients' sera compared to control subjects. Human Apoptotic Array revealed an increased expression of five apoptotic proteins: BIM, CD40, IGFBP2, P21, and SMAC, following sera incubation of non-chronic pediatric ITP patients, compared to chronic patients' sera, at diagnosis. Our data contribute to knowledge on apoptosis markers that may aid in predicting the prognosis of children with ITP. The key message of our article is that children with chronic ITP have a different apoptotic profile compared to non-chronic ITP. Addition to existing literature: This is the first study comparing apoptotic markers between children with chronic ITP to non-chronic ITP. Our findings indicate that, in the future, apoptotic markers may help to classify ITP patients into non-chronic versus chronic ones, at diagnosis.

Роль биопленок в развитии и хронизации ЛОР-патологии и способы воздействия на них

The improvement of treatment efficacy for any disorder, including infectious diseases, is one of the most important tasks for current medicine. One of possible ways to achieve it is to find some therapeutic agents that can affect microbial biofilms, since they have been shown to play an important role in the development of 80% of diseases, including chronic ones. So far, there have been no optimal methods of destroying biofilms. In this article, we discuss non-antibiotic treatments with antibiofilm activity in the upper respiratory tract mucosa. Essential oils (EOs) and their complexes are a promising treatment for patients with infectious diseases. They have been used in dental and gynecological practice, treatment of infections of the urinary and upper respiratory tracts (rhinitis, sinusitis, nasopharyngitis) and demonstrated their effectiveness. The antibacterial activity of EOs from plants depends on the complexity of the composition of a specific EO complex and the type of microorganism. We provide the evidence of the efficacy of the EO complex "Maslo Dyshi" (Akvion, Russia), whose antibiofilm activity was demonstrated by Russian scientists on the model with mycobacterial (MBT) biofilms and compared with EOs used alone (eucalyptus, pine, bergamot). The authors proved complete suppression of various biofilm states in all studied MBT strains exposed to vapors of the EO complex "Maslo Dyshi" (high antibacterial and antibiofilm activity), probably associated with the synergistic effect of EOs included in the complex. The bactericidal activity of a similar EO composition was evaluated in a German study, which demonstrated that mint and cajuput oils had the highest activity. This study also ranked activity of all EOs included in a complex similar in its composition to "Maslo Dyshi" and emphasized its association with the exposure time and concentration, since EOs evaporate over time. We discuss the results of studies that demonstrated virucidal activity of "Maslo Dyshi" against influenza virus, rhinovirus, adenovirus, and respiratory syncytial, as well as its clinical activity. All authors reported decreased frequency and duration/number of complications of viral infections, including that in children with frequent respiratory infections. New data on the antibiofilm activity of this EO complex opens new horizons for its use in outpatient clinical practice. Key words: biofilm, children with frequent respiratory infections, acute respiratory infections

To the pathological anatomy of bulbar paralysis of vascular origin

Bulbar paralysis has long been attracting the attention of neuropathologists, due to its diversity in the clinical picture, the duration of the course of the disease and the severity of the disease. In Germany, the term bulbar paralysis was first used in 1864 by Wachsmuth in relation to the chronic form, which is now called Duschenns progressive bulbar paralysis. Due to the difficulties of recognition, cases of intravital diagnosis of paralysis with lesions of the medulla oblongata were almost absent at that time. In France, the acquaintance with this disease began, apparently, a little earlier than Germany, but there and here they soon began to distinguish acute cases (Lange) of paralysis from chronic ones.

Analysis of electropharmacological and proarrhythmic effects of donepezil using the halothane-anesthetized intact dogs and the conscious chronic atrioventricular block ones.

Donepezil, an inhibitor for acetylcholinesterase used for patients with Alzheimer's disease, has been shown to inhibit IKr, occasionally inducing torsade de pointes. In order to analyze the causal relationship between donepezil treatment and onset of lethal arrhythmias, we initially assessed electropharmacological effects of donepezil hydrochloride of 0.01, 0.1, and 1 mg/kg, i.v. over 10 min using the halothane-anesthetized intact dogs (n = 4), possibly providing subtherapeutic to supratherapeutic plasma concentrations. Although the low or middle dose did not exert any effect, the high dose transiently increased the ventricular refractoriness along with modest prolongation of the late repolarization period, indicating potential IKr inhibitory action in vivo. Moreover, the high dose induced the positive chronotropic, inotropic, and dromotropic actions along with the pressor effect and prolongation of early repolarization period, suggesting sympathicotonic condition in the central nervous system. Next, we examined proarrhythmic effects of donepezil hydrochloride of 0.1 and 1 mg/kg, i.v. over 10 min using the conscious chronic atrioventricular block dogs (n = 4). Although the low dose hardly affected the cardiovascular variables, the high dose increased the atrial and ventricular rate without significantly altering the repolarization period, possibly reflecting sympathicotonic condition. Importantly, the high dose induced non-sustained ventricular tachycardia in half of the animals. Thus, donepezil by itself did not induce torsade de pointes in vivo, which suggests that donepezil-induced sympathicotonic condition may induce Ca2+ overload, triggering the ventricular arrhythmias, but might indirectly attenuate its IKr inhibitory action, preventing excessive repolarization delay.

Diabetes mellitus

Diabetes mellitus is a complex group of chronic diseases with different etiology, clinical course and evolution, in which hyperglycemia is their common link, triggering defects in insulin secretion and/or its mechanism of action causing disorders in distinct organs and systems. Diabetes is classified according with its etiology, highlighting type 1 and type 2 diabetes mellitus, gestational diabetes, and other types, mainly monogenic diabetes (MODY) or associated to other conditions. A rapid onset of hyperglycemia can cause acute complications (diabetic ketoacidosis, hypoglycemia), or chronic ones occurring mainly both at the micro- (retinopathy, nephropathy, neuropathy) and at the macrovascular level (ischemic heart disease, stroke, peripheral arterial disease). Diagnostic criteria are based on fasting blood glucose, postprandial blood glucose and glycated hemoglobin levels, distinguishing among prediabetes or diabetes. Deeper medical assessment is required in order to know the baseline status of the patient to detect comorbidities and vascular complications already present. Patient has to be trained in the diabetes management from the beginning, and follow-up planning has to be stablished.