One drug to treat many diseases: unlocking the economic trap of rare diseases.

There are two major problems with the development of therapies for rare diseases. First, among over 7000 such diseases, the vast majority are caused by genetic defects and/or include neurodegeneration, making them very difficult to treat. Second, drugs for rare diseases, so-called orphan drugs, are extremely expensive, as only a small number of patients are interested in purchasing them. This results in the appearance of a specific economic trap of rare diseases; namely, despite high biomedical, pharmaceutical and technological potential, the development of new orphan drugs is blocked by the economic reality. The purpose of this work was to find a potential solution that might resolve this economic trap of rare diseases. A literature review was conducted, and a hypothesis was formulated assuming that the use of one drug for the treatment of many rare diseases might overcome the economic trap. We provide examples showing that finding such drugs is possible. Thus, a possible solution for the problem of developing orphan drugs is presented. Further preclinical and clinical studies, although neither easy nor inexpensive, should verify whether the hypothesis regarding the possibility of unlocking the economic trap of rare diseases is valid.

Acyclovir inhibits Cyprinid herpesvirus 3 multiplication in vitro.

Cyprinid herpesvirus 3 (CyHV-3), also known as koi herpesvirus (KHV), is an aetiological agent of a virulent and lethal disease in common and koi carp. In this study, we examined in vitro the anti-CyHV-3 activity of acyclovir (ACV), nucleoside analogue commonly used against human herpesviruses, as well as acyclovir monophospate (ACV-MP). The cytotoxicity of the ACV and the ACV-MP for two common carp cell lines, CCB (Common carp brain) and KF1 (Koi carp fin 1), was determined by means of MTT and crystal violet assays. In subsequent studies, the concentration of 66.67 µM was applied. The ACV and the ACV-MP (66.67 µM) inhibited a cytopathic effect (CPE) induced by the CyHV-3 virus in the CCB (ACV by 66%, ACV-MP by 58%) and the KF1 (ACV by 25%, ACV-MP by 37%). The viral load measured by the means of TaqMan qPCR was reduced in a range of 67%-93% depending on the analogue, the cell line and the time of incubation. The expression of viral genes (ORF149, ORF3, ORF134 and ORF78) in CCB cells infected with the CyHV-3 was strongly downregulated within the range of 78%-91%. In summary, both the ACV and the ACV-MP can inhibit CyHV-3 replication in vitro.

Hematological Alterations as a Response to Exposure to Selected Fungicides in Common Carp (Cyprinus carpio L.).

The aim of the present study was to assess the hematological response of common carp to fungicides and to determine recovery patterns in fungicide-free water. Fish were exposed to mancozeb, prochloraz or tebuconazole (at concentrations of 1.0, 1.0 and 2.5 mg 1⁻¹, respectively) for 14 days followed by a 30-day recovery period. The following hematological parameters were examined after 1, 3 and 14 days of exposure as well as after recovery time: red blood cells (RBC), hematocrit (Het), total hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), total number of leukocytes (WBC) and leukograms. All analyzed parameters revealed alterations in relation to control samples. The pattern of these changes was irregular, showing either an increase or decrease at different time points of the experiment and not all observed differences were statistically significant. The most noticeable fungicide-specific changes were,observed on the 1st and 14th days of chemical exposure. The majority of the parameters under investigation returned to the control levels after a detoxication period. However, some of the exerted effects were irreversible (Hb, MCH, MCHC and WBC for fish subjected to mancozeb; Hb, MCH, MCHC and monocyte count for fish subjected to prochloraz; Hct and monocyte number for fish subjected to tebuconazole). All of the observed hematoloaical changes were not toxin-soecific.

[Advantages and disadvantages of microbiological methods used in the diagnosis of Mycoplasmapneumoniae infections in selected clinical situation]. / Wady i zalety mikrobiologicznych metod diagnostycznych stosowanych w rozpoznaniu zakazenia wywolanego przez Mycoplasma pneumoniae na przykladzie wybranej sytuacji klinicznej.

Mycoplasma pneumoniae is one of the most common causes of community-acquired pneumonia in children and adults. Correct and rapid laboratory diagnosis of M pneumoniae infections is important to introduce appropriate antibiotic treatment. Diagnosis for M. pneumoniae usually relies on serological tests and/or molecular investigations. Both methods have some advantages but also limitations. This paper presents advantages and disadvantages of microbiological methods used in M. pneumoniae infection an example of case of patient with mycoplasmosis.

[Etiology of bacterial infections and incidence of comorbidities in patients with tuberculosis, treated in Mazovian Treatment Centre of Tuberculosis and Lung Diseases during years 2012-2014].

INTRODUCTION: Tuberculosis (TB) is an infectious disease caused by the Mycobacterium tuberculosis. Infection occurs mostly via inhalation, while the immune system is weakened. TB can take a pulmonary or extrapulmonary form. Treatment involves an intensive, long-term antimycobacterial multidrug therapy. TB cases are recorded on the worldwide scale. The morbidity in Poland varies territorially. AIM: The analysis of bacterial infections and comorbidities cases in the patients with TB, treated in Mazovian Treatment Centre of Tuberculosis and Lung Diseases (MCLChPiG) during years 2012-2014. MATERIALS AND METHODS: The study includes an analysis of 3093 cases of tuberculosis among MCLChPiG patients in years 2012-2014, taking into account the age and gender of patients, forms of the disease, bacterial superinfection in the course of TB (based on the results of microbiological tests) and concomitant diseases. RESULTS: The study showed that TB was more common in men (64.79%). Most cases have been diagnosed in the 50-65 year age group (31.65%). The most common form of TB among MCLChPiG patients was a respiratory tract tuberculosis (96.61%), especially the pulmonary form (82.67%). Concomitant diseases were diagnosed in 244 patients (7.89%), wherein tumors (4.88%) were the most common ones. Bacterial superinfection in the course of TB was observed in 149 patients (4.82%). The most frequently isolated bacteria were H. influenzae (28.65%) and S. aureus (15.79%). CONCLUSIONS: Long-term antimycobacterial treatment leads to the weakening of the patient's immune system, which is a favorable condition for the development of bacterial infections. Superinfection can be associated with concomitant disease, where weakness of immunoresponsiveness increases the risk of developing TB. Bacteria isolated from superinfections in the course of TB are mostly a typical pathogens of the upper and lower respiratory tract.

Reactions of N(3) -substituted amidrazones with cis-1,2-cyclohexanedicarboxylic anhydride and biological activities of the products.

A series of novel compounds were synthesized in reactions of N(3) -substituted amidrazones with cis-1,2-cyclohexanedicarboxylic anhydride: linear, isoindole, and triazole derivatives. All new structures were confirmed by H(1) NMR and IR spectrometry as well as elemental analysis. Potential biological effects of new compounds were predicted with the Prediction of Activity Spectra for Substances (PASS) program. Antiviral, antibacterial, analgesic, and anti-inflammatory activities were experimentally verified.

[The role of cytokines in depression]. / Rola cytokin w depresji.

Clinical and experimental studies on animals indicate that depression is associated with increased plasma cytokine acute phase protein concentrations and hypothalamic-pituitary-adrenal axis (HPA) activation. Additionally it has been detected that immunological activation induces stress-like behavioural and neurochemical changes in organisms of animals and humans. Hypersecretion of cytokines in response to stress or to endogenous trigger factors may induce depressive symptoms. Corticotropin releasing hormone (CRH) overproduction in the brain also may participate in cytokine-induced behavioural and neurochemical changes. Treatment with antidepressants conferred protection against cytokine-induced depressive-like biological and behavioural changes. This is mainly due to alterations of the pro-/anti-inflammatory cytokine balance. There is a substantial body of evidence that the immune system plays a major role in aetiology of depression and that cytokines participate in neurochemical, behavioural and endocrine changes in this illness.

Serum cytokine level and production of reactive oxygen species (ROS) by blood neutrophils from a schizophrenic patient with hypersensitivity to neuroleptics.

BACKGROUND: There have been few publications concerning the role of the immune system in neuroleptic intolerance. Some studies have shown that in neuroleptic malignant syndrome (NMS), associated with disseminated intravascular coagulation (DIC), the serum level of tumor necrosis factor alpha (TNF-alpha) increases significantly, which is thought to trigger the onset of DIC. CASE REPORT: A 23-year-old woman suffering from catatonic schizophrenia developed hypersensitivity to neuroleptics. One month before being referred to the present authors, she had a haloperidol-induced NMS episode in another psychiatric hospital, with high temperature, CPK activity, muscle rigidity and leukocytosis. On admission to our clinic and after treatment with promazine, laboratory tests showed an increase in serum CPK activity and mild leukocytosis. Neuroleptic treatment was discontinued, and the serum level of CPK and white blood cell count was monitored daily for 7 days, as well as the serum level of some cytokines and the production of reactive oxygen species (ROS) by blood neutrophils. The serum levels of interleukin 1 alpha (IL-1), IL-6 and TNF-alpha changed significantly over the observation period, forming waves with peak activity of IL-6 and TNF-alpha exceeding normal levels. The level of IL-1 alpha was within the control range. ROS production by the patient's blood neutrophils was also increased, as well as catalase serum activity. CONCLUSIONS: Some proinflammatory cytokines may participate in the mechanisms leading to the development of neuroleptic intolerance in schizophrenic patients. Cytokine-stimulated ROS production may participate in tissue injury and increase CPK serum activity.

Changes in serum concentrations and in cytokine production by blood cell cultures of a patient with major depression--case report.

The aim of the paper was to compare the periodical changes in serum cytokine levels and in cytokine production in short-term blood lymphocyte cultures of two persons: the patient with major depression and healthy control. In sera of both persons such cytokines as IL-1 beta, IFN-gamma and IL-6 were detected, but IL-6 level in serum of depressed patient was higher than that observed in healthy control. In both persons examined serum cytokine level changed periodically during 9 days of observation showing rhythmic waves. When cytokines were induced in lymphocyte cultures periodical changes in their production were also observed, but IL-1 alpha, IL-1 beta and IL-12 production was significantly lower in comparison to lymphocytes of healthy control. After 36 days of medical treatment cytokine levels in serum of patient normalized, except for IL-12. Our results suggest that inconsistence in the data from papers of different authors concerning cytokine production in major depression could result from periodical changes in their level and from the fact that patients were examined at the time when certain cytokine was near its peak or declined significantly. The rhythmic changes in cytokine level should be taken into consideration when the role of cytokines in major depression is examined.