Depression and Cognitive Dysfunction in Patients with Chronic Hepatitis C: Correlation with Viral Replication in the Peripheral Blood Mononuclear Cells and Cytokines in Serum.

Chronic hepatitis C virus (HCV) infection is commonly associated with depression and cognitive dysfunction, the cause of which could be related to the HCV neuroinvasion and/or state of chronic inflammation. Viral sequences and proteins were previously detected in the brain and since blood leukocytes can cross the blood-brain barrier, they could provide viral access to the CNS. Eighty chronic hepatitis C patients were tested for viral replication in PBMCs (detection of the HCV RNA-negative strand) and serum cytokines. Depression was assessed by the Beck Depression Inventory (BDI), neuroticism by the Eysenck Personality Inventory (N/EPO-R), and anxiety by the State-Trait Anxiety Inventory (STAI) while neurocognitive testing included the Wisconsin Card Sorting Test (WCST), Ruff Figural Fluency Test (RFFT), California Verbal Learning Test (CVLT), and Grooved Pegboard Test (GPT). The HCV RNA-negative strand was detected in PBMCs from 24 (30%) patients and these patients had significantly higher BDI scores (median 12.5 [IQR] 6.3-20.5 vs. median 8.00 [IQR] 3-12; p = 0.013). Both depression and anxiety correlated positively with IL-8 while cognitive flexibility, executive function, problem-solving skills, memory, and motor functioning correlated negatively with some proinflammatory cytokines. Our findings suggest that due to chronic HCV infection, the brain function is negatively affected by both viral replication in PBMCs and by the immune activation state.

Higher platelet counts correlate to tumour progression and can be induced by intratumoural stroma in non-metastatic breast carcinomas.

BACKGROUND: Platelets support tumour progression. However, their prognostic significance and relation to circulating tumour cells (CTCs) in operable breast cancer (BrCa) are still scarcely known and, thus, merit further investigation. METHODS: Preoperative platelet counts (PCs) were compared with clinical data, CTCs, 65 serum cytokines and 770 immune-related transcripts obtained using the NanoString technology. RESULTS: High normal PC (hPC; defined by the 75th centile cut-off) correlated with an increased number of lymph node metastases and mesenchymal CTCs in the 70 operable BrCa patients. Patients with hPC and CTC presence revealed the shortest overall survival compared to those with no CTC/any PC or even CTC/normal PC. Adverse prognostic impact of hPC was observed only in the luminal subtype, when 247 BrCa patients were analysed. hPC correlated with high content of intratumoural stroma, specifically its phenotype related to CD8+ T and resting mast cells, and an increased concentration of cytokines related to platelet activation or even production in bone marrow (i.e. APRIL, ENA78/CXCL5, HGF, IL16, IL17a, MDC/CCL22, MCP3, MMP1 and SCF). CONCLUSIONS: Preoperative platelets evaluated alone and in combination with CTCs have prognostic potential in non-metastatic BrCa and define patients at the highest risk of disease progression, putatively benefiting from anti-platelet therapy.

Loneliness and mental health among the elderly in Poland during the COVID-19 pandemic.

BACKGROUND: The unexpected changes caused by the COVID-19 pandemic related to the fear of developing the disease, and the need for social distancing and isolation have had an effect on people's mental health. These drastic changes can result in the development of anxiety, depressive symptoms and sense of loneliness. Elderly and chronically ill individuals are at a particularly high risk of developing COVID-19, suffering severe illness and dying as a result of it. AIM OF THE STUDY: The aim of the study was to assess the prevalence of anxiety, depressive symptoms, irritability and loneliness in the elderly aged 60 years and older as a group exposed to the negative impact of the COVID-19 pandemic, and to analyze the relationships between loneliness and mental health of the respondents and sociodemographic variables and chronic diseases. MATERIALS AND METHODS: The study was conducted in Poland among 221 individuals aged 60+. The study material was collected using a sociodemographic questionnaire, Hospital Anxiety and Depression Scale (HADS-M) and a revised University of California Los Angeles loneliness scale (R-UCLA). Women accounted for 47.51% and men for 52.49% of study participants; the mean age was 65.18 (SD = 4.06). RESULTS: In total, according to HADS-M, depressive symptoms were present in 19.15% of the participants and borderline states in 14.18% of them. Based on R-UCLA, moderate and moderately high sense of loneliness was present in 58.83% of the participants. Sense of loneliness was significantly correlated with the prevalence of depressive symptoms (p < 0.001). CONCLUSIONS: In this study, one in five participants experienced anxiety and depressive symptoms. Two out of three participants experienced a moderate sense of loneliness. Individuals who displayed a higher level of loneliness also had a higher severity of anxiety level depressive symptoms and irritability. Elderly individuals should be under special care due to their high risk of experiencing physical and mental effects of the COVID-19 pandemic.

Relationship between loneliness and blood glucose control in diabetes.

BACKGROUND: The data of the International Diabetes Federation show that about 463 million people have diabetes. Better understanding of psychosocial aspects of life with this disease has become one of healthcare priorities in this group of patients. The aim of this study was to assess the relationships between loneliness and blood glucose control in diabetic patients. METHODS: The study included 250 hospitalized patients with type 1 and 2 diabetes. The patients included in the study were those who had had diabetes for at least 1 year and received pharmacotherapy. Standardized Revised UCLA Loneliness Scale (R-UCLA) and an analysis of patient test results including 10 indicators of blood glucose control were used for data collection. Correlation analysis, i.e. Pearson's linear correlation coefficient (r, parametric method), was used for hypothesis verification. RESULTS: Less than one-fifth (16%) of the patients included in the study had higher loneliness index (based on the R-UCLA scale), and this loneliness index (total result) was significantly correlated with higher blood pressure. No significant correlations were demonstrated between loneliness and the other 9 indicators of blood glucose control. CONCLUSIONS: Systolic blood pressure was significantly correlated with loneliness in patients with diabetes. Further studies are needed to confirm these findings.

Worse survival in breast cancer in elderly may not be due to underutilization of medical procedures as observed upon changing healthcare system in Poland.

BACKGROUND: Evidence is emerging that older women may tolerate breast cancer therapies equally well as the young ones, providing that they receive good supportive care. It has also been reported that these patients remain outside the current therapeutic standards. The aim of this observational study was to assess the access of breast cancer patients to medical procedures. METHODS: We retrospectively reviewed a database of breast cancer patients registered in the National Cancer Registry in Poland, searching for the numbers of new cases and deaths in the years 2010-2015. We obtained the numbers and costs of key medical procedures provided for these patients from the National Health Fund in Poland. Breast cancer survival in the years 2010-2015 was estimated based on the mortality/incidence ratio. The t-Student test and Spearman correlation coefficient were used for the analysis of data obtained from both databases. RESULTS: There was no increase in survival throughout the years 2010-2015 in both analysed subpopulations of all breast cancer patients below and over 65 years of age, despite an unprecedented rise in healthcare funding in Poland. We noted 37% lower probability of 5-year survival in patients older than 65 years. The average number of outpatient visits and surgical procedures per person per year were slightly, yet significantly (p < 0.01), higher in younger vs. older patients (3.9 vs. 3.4 and 1.18 vs. 1.02, respectively). Outpatient chemotherapy was more common in older patients (6.0 vs. 5.25 cycles a year per person on average, p < 0.01). There were no significant differences in the average numbers of hospitalisations for chemotherapy, frequencies of radiotherapy and in the use of targeted therapy programmes (calculated per person per year), between younger and older patients. CONCLUSIONS: Older women with breast cancer are treated similarly to younger patients, but have significantly worse chances to survive breast cancer in Poland. A simple increase in healthcare financing will not improve the survival in the elderly with breast cancer without developing funded individualised care and survivorship programmes.

Salivary interleukin 6, interleukin 8, interleukin 17A, and tumour necrosis factor α levels in patients with periodontitis and rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) and periodontitis share risk factors and inflammatory pathways that could be related to cytokines, such as interleukin (IL)-6, IL-8, IL-17A, and tumour necrosis factor-α (TNF-α). The aim of this study was to compare periodontal status and salivary levels of selected cytokines between patients diagnosed with RA and periodontitis. RA patients were assessed for the potential influence of anti-rheumatic therapy. MATERIAL AND METHODS: One hundred and six patients were enrolled in a cross-sectional study. Medical assessment and periodontal examination were performed in 35 patients with chronic periodontitis, in 35 patients with RA and chronic periodontitis, and in 36 controls. Unstimulated whole saliva samples were analysed for IL-6, IL-8, IL-17A, and TNF-α. RESULTS: Significant differences in biomarkers and periodontal parameters were found among groups. Study groups exhibited higher mean pocket depth (PD), number of PD > 4 mm, and mean clinical attachment loss, when compared with controls. The RA group had lower bleeding on probing index and PD, but higher values of plaque indices than the periodontitis group. Concentration of evaluated cytokines were higher in the RA and periodontitis groups, compared with controls. The periodontitis group showed also higher levels of IL-6, IL-17A, and TNF-α in comparison to RA. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticosteroids. CONCLUSIONS: Salivary levels of IL-6, IL-8, IL-17A, and TNF-α can be affected by periodontitis, RA, and presumably DMARDs. DMARD therapy appears to reduce destructive and inflammatory processes in periodontal tissues because lower values of PD, BOP, and salivary levels of IL-6, IL-17A, and TNF-α were found in RA.

Monitoring of in vitro dynamics of Acanthamoeba strains isolated from infected eyes as a useful tool in keratitis management.

Free-living amoebae of Acanthamoeba genus are ubiquitous in various parts of the world. Some species of these amoebozoans present a serious risk to human health as the causative agents of vision-threatening diseases, Acanthamoeba keratitis. Correct diagnosis requires both a clinical examination of the cornea and amoebic form identification in affected eyes. Despite advances in pharmacotherapy, the infection is difficult to diagnose and to threat. Population dynamics of five different Acanthamoeba strains cultured in vitro under bacteria-free condition in BSC medium, was monitored in terms of diagnostic and therapeutic management. The range of protozoan number in the exponential growth phase, the morpho-physiological status of amoeba forms and their ability to multiply were evaluated. Results of the studies revealed that early and continued monitoring of the strains maintained in an axenic culture showed correlation between the dynamics of cultivated amoebae and the course of the disease, differences in response to pharmacotherapy and the surgical management efficacy. Concluding, the in vitro monitoring of dynamics of Acanthamoeba strains isolated from infected corneas may be important not only for proper diagnosis but also as a useful tool in keratitis management and therapeutic prognosis.

NMR spectroscopy of human eye tissues: a new insight into ocular biochemistry.

BACKGROUND: The human eye is a complex organ whose anatomy and functions has been described very well to date. Unfortunately, the knowledge of the biochemistry and metabolic properties of eye tissues varies. Our objective was to reveal the biochemical differences between main tissue components of human eyes. METHODS: Corneas, irises, ciliary bodies, lenses, and retinas were obtained from cadaver globes 0-1/2 hours postmortem of 6 male donors (age: 44-61 years). The metabolic profile of tissues was investigated with HR MAS 1H NMR spectroscopy. RESULTS: A total of 29 metabolites were assigned in the NMR spectra of the eye tissues. Significant differences between tissues were revealed in contents of the most distant eye-tissues, while irises and ciliary bodies showed minimal biochemical differences. ATP, acetate, choline, glutamate, lactate, myoinositol, and taurine were identified as the primary biochemical compounds responsible for differentiation of the eye tissues. CONCLUSIONS: In this study we showed for the first time the results of the analysis of the main human eye tissues with NMR spectroscopy. The biochemical contents of the selected tissues seemed to correspond to their primary anatomical and functional attributes, the way of the delivery of the nutrients, and the location of the tissues in the eye.

Military Blood Service in Poland.

Introduction: On 24 February 2022, the Russia-Ukraine military conflict unfolded just across the eastern border of the European Union. It made everyone realize how important it is to secure blood supplies to health-care units in the event of an armed conflict. This paper presents the principles of functioning of the Military Blood Donation Service and the Military Center for Blood Donation and Hemotherapy in Poland. Methods: The study used data collected in the "Military Blood Bank" information processing system and data from annual reports (2010-2021) sent to the Minister of Health of the Republic of Poland. The reports concerned, among others: demographic data on donors, reasons of permanent disqualifications, numbers of complete and incomplete donations, etc. Results: Since 2005, the number of donors registered in military blood donation centers ranged between 15 and 35 thousand/year. The most dramatic declines in donors were observed in 2010 and 2020. Successful donations accounted for more than 98% of all donations/year (except 2015), and their number varied between 20 and 32 thousand/year. Among the blood donors, men always predominated and the dominant age group (except for 2010) was 25-44 years. The reasons for permanent disqualification have varied over time: their proportions decreased for viral hepatitis and cardiovascular disease, and increased for respiratory and endocrine/metabolic diseases. Due to the COVID-19 pandemic in 2020/2021, these proportions have sometimes been reversed. Discussion: The Military Blood Donation Service has been functioning in Poland for several decades. It is specialized in supplying blood and blood products to the Armed Forces. Unfortunately, it was not possible to refer to the functioning of similar institutions in other countries. Therefore, when evaluating the functioning of Polish military blood donation, we had to rely on numerical values (eg, number of donors/year, donor profile, etc.), which prove a very good organization of blood donation centers. However, it should be noted that, as in other countries, a more active promotion of blood donation in the media is advisable in order to encourage as many young people as possible to donate blood.

Cytokine profile and viral diversity in the early seronegative stage of community-acquired hepatitis C virus (HCV) infection.

Most Hepatitis C virus (HCV)-infected subjects develop chronic infection, whereas a minority clear the virus in the early phase of infection. We analyzed factors associated with outcome (chronicity vs clearance) during the preclinical seronegative phase of community-acquired HCV infection. Among 17.5 million blood donations in the years 2000-2016, 124 blood donors were found to be HCV RNA-positive/anti-HCV-negative. All were contacted after 0.5-12.7 years and 40 responded and provided blood sample. Hypervariable region 1 was analyzed by ultradeep pyrosequencing and cytokines in serum were quantified by Luminex (R&D Systems) multiplex immunoassay. Twenty-one (52.5%) donors were found to be HCV-RNA-positive, while 19 (47.5%) were HCV RNA negative (none received antiviral treatment). All but one seroconverted to anti-HCV. Donors with resolving hepatitis did not differ significantly from donors with chronic infection with respect to age, genotypes, IL28B polymorphisms, number of viral variants, nucleotide diversity per site or the overall number of nucleotide substitutions. However, the former group had significantly higher levels of IL-1beta, IL-1RA, IL-6, IFN-gamma and FGF-2 in serum. In our study of community-acquired acute hepatitis C approximately half of all subjects eliminated the virus spontaneously, and this clearance was associated with marked cytokine response in the early seronegative stage of infection.

Human Milk Oligosaccharides Exhibit Biofilm Eradication Activity Against Matured Biofilms Formed by Different Pathogen Species.

Human milk oligosaccharides (HMOs) have been shown to exhibit plenty of benefits for infants, such as prebiotic activity shaping the gut microbiota and immunomodulatory and anti-inflammatory activity. For some pathogenic bacteria, antimicrobial activity has been proved, but most studies focus on group B streptococci. In the present study, we investigated the antimicrobial and antibiofilm activities of the total and fractionated HMOs from pooled human milk against four common human pathogenic Gram-negative species (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cenocepacia) and three Gram-positive species (Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis). The activity of HMOs against enterococci and B. cenocepacia are addressed here for the first time. We showed that HMOs exhibit a predominant activity against the Gram-positive species, with E. faecalis being the most sensitive to the HMOs, both in planktonic bacteria and in biofilms. In further tests, we could exclude fucosyllactose as the antibacterial component. The biological significance of these findings may lie in the prevention of skin infections of the mother's breast as a consequence of breastfeeding-induced skin laceration and/or protection of the infants' nasopharynx and lung from respiratory pathogens such as staphylococci.

Actual and perceived knowledge of type 1 diabetes mellitus among school nurses.

BACKGROUND: In general, school nurses are aware that it is important to have knowledge of type 1 diabetes to give adequate care to children with the disease. Many studies assessing diabetes knowledge have found different deficits among nurses. To our knowledge, however, no study has assessed the knowledge of type 1 diabetes among school nurses. OBJECTIVE: To assess actual and perceived diabetes knowledge among school nurses. DESIGN: Cross-sectional studies. SETTINGS: Seventeen primary care facilities in Warsaw that employed school nurses. PARTICIPANTS: Two hundred and thirty school nurses. METHODS: With the Diabetes Knowledge Questionnaire (DKQ), we assessed actual diabetes knowledge. With the Self-Assessed Diabetes Knowledge (SADK), we assessed perceived diabetes knowledge. Both the DKQ and SADK assessed seven domains of diabetes knowledge: general diabetes knowledge; insulin and glucagon; insulin pumps; diabetes complications; nutrition; physical activity, stress, and comorbidities; and glycemia measurements. We related DKQ and SADK scores to each other and to sociodemographic and work-related factors. RESULTS: The rate of correct responses in the DKQ was 46.7%, with the lowest rate regarding knowledge of insulin pumps (36.5%), nutrition (37.4%), and insulin and glucagon (37.9%). Actual and perceived diabetes knowledge were moderately positively correlated (rho = 0.18, p =.009). In six of the seven knowledge domains examined, school nurses perceived their diabetes knowledge better compared with their actual knowledge. DKQ scores were higher in nurses with higher education (p = .024), those who had relatives or friends with diabetes (p = .032), and those who had prior diabetes training (p = .050). Interestingly, DKQ scores were higher among nurses with fewer years of experience (rho = - 0.18, p = .011). CONCLUSIONS: There is a need for additional diabetes training among nursing students and practicing nurses to provide safe and effective care for children with type 1 diabetes.

The pro-tumor effect of CD200 expression is not mimicked by agonistic CD200R antibodies.

Tumor-infiltrating immune cells can impact tumor growth and progression. The inhibitory CD200 receptor (CD200R) suppresses the activation of myeloid cells and lack of this pathway results in a reduction of tumor growth, conversely a tumorigenic effect of CD200R triggering was also described. Here we investigated the role of CD200R activation in syngeneic mouse tumor models. We showed that agonistic CD200R antibody reached tumors, but had no significant impact on tumor growth and minor effect on infiltration of immune myeloid cells. These effects were reproduced using two different anti-CD200R clones. In contrast, we showed that CD200-deficiency did decrease melanoma tumor burden. The presence of either endogenous or tumor-expressed CD200 restored the growth of metastatic melanoma foci. On the basis of these findings, we conclude that blockade of the endogenous ligand CD200 prevented the tumorigenic effect of CD200R-expressing myeloid cells in the tumor microenvironment, whereas agonistic anti-CD200R has no effect on tumor development.

Effect of gamma-irradiation on cladribine and cladribine-containing biodegradable copolymers.

The aims of this study were to assess the effects of sterilization with gamma-irradiation on (i). bulk cladribine and (ii). cladribine-containing biodegradable copolymers. The stability of cladribine upon irradiation was confirmed by TLC, HPLC, UV, IR, DSC, rentgenography and electron microscopy. The stability of copolymers containing cladribine upon irradiation was assessed by IR, DSC and EPR. In vitro kinetics of nucleoside release from the copolymers before and after irradiation were compared, and only slight changes were found. Results of our study indicate that gamma-irradiation can be safely applied for the sterilization of cladribine or cladribine-containing copolymers for medical purposes.

5'-Esters of 2'-deoxyadenosine and 2-chloro-2'-deoxyadenosine with cell differentiation-provoking agents.

Phenylacetic and retinoic acids are carboxyacidic cell differentiating agents displaying anticancer activities. We report on a new class of compounds including the 5'-esters of 2'-deoxyadenosine (dA) or 2-chloro-2'-deoxyadenosine (cladribine, 2CdA) and the aforementioned acids. The rationale behind the synthesis of these esters was that if they are hydrolyzed inside the lymphoid cells, either dA will be removed from the intracellular environment by deamination, or 2CdA will be phosphorylated and accumulated. In either case targetted delivery of the differentiating agent to the lymphoid cells may be envisaged. The said compounds were synthesized by the Mitsunobu procedure employing triphenylphosphine and azadicarboxylic acid esters, and their stability was tested against various esterases. Esters of dA and 2CdA with phenylacetic acids were found to be resistant to enzymatic hydrolysis, whereas those with retinoic acids were efficiently hydrolyzed by commercially available hepatic esterase as well as by esterases present in the blood plasma and in diluted human lymphocyte lysate. Susceptibility to enzymatic hydrolysis was found to be a prerequisite of cytotoxic and/or differentiating activity of these esters in leukemic cell lines.

In vitro release of cytotoxic nucleoside analogs from lactide-caprolactone and lactide-glycolide copolymers.

The aims of our study were to assess the release of cytotoxic nucleoside analogs 5-fluorouracil and 2-chloro-2'-deoxyadenosine from different lactide-glycolide or lactide-caprolactone biodegradable copolymers and the effects of sterilization on this release. The polymers were sterilized either with ethylene oxide at 37 degrees C, or with gamma radiation (15 kGy, 20 kGy, or 25 kGy). The kinetics of nucleoside release from the copolymers were measured over 50 days. Four copolymers exhibited relatively constant release of nucleosides in micromolar concentrations during the entire observation period. Sterilization with either ethylene oxide or gamma radiation only slightly influenced nucleoside release. Further development of these copolymers as an intracerebral nucleoside delivery system for local treatment of brain tumors is indicated.

Expansion of the Golgi apparatus in rat cerebral cortex following intracerebroventricular injections of streptozotocin.

Streptozotocin (STZ) is a bacterial toxin which selectively damages both insulin-producing cells and insulin receptors. Injections of STZ into the cerebral ventricles of experimental animals are followed by sustained biochemical, metabolic and behavioral effects resembling those which are found in human brains afflicted by Alzheimer's disease. The aim of the present study was to assess the effects of double intracerebroventricular application of STZ on the ultrastructure of rat frontoparietal cortical neurons. The most prominent change, seen 3 weeks after STZ injection, was a significant enlargement of the Golgi apparatus caused by expansion of the trans-Golgi segment of the cellular protein secretory pathway. Morphometric analysis revealed that the area of the trans part of the Golgi complex in neuronal cells was increased more than two-fold (median values: 312 x 10(3) nm in 14 neurons from control animals, and 846 x 10(3) nm3 in 19 neurons from STZ-treated animals, P = 0.0012), whereas that of the cis part did not significantly change. The effects of STZ did not resemble Golgi atrophy and fragmentation described in neurons from disease-prone brain structures of patients with Alzheimer's disease, but were similar to that observed after intravenous application of a non-metabolizable glucose analog 2-deoxyglucose. Considering that proamyloidogenic processing of beta-amyloid precursor protein may occur preferentially in the trans-Golgi segment, the observed early response of neuronal ultrastructure to desensitization of insulin receptors may predispose cells to form beta-amyloid deposits.

2-deoxyglucose induces beta-APP overexpression, tau hyperphosphorylation and expansion of the trans-part of the Golgi complex in rat cerebral cortex.

The effects of a single intraperitoneal injection of a non-metabolizable glucose analog 2-deoxyglucose (2-DG, 500 mg/kg) on the levels of beta-APP expression, and phosphorylated and unphosphorylated tau protein in the rat cerebral cortex were investigated. The effects of 2-DG on the ultrastructure of cortical neurons with particular emphasis on the morphology of the Golgi apparatus, and on brain bioenergetics assessed by in vivo 31P-MRS technique were also evaluated. Seven and a half hours after injection of 2-deoxyglucose a significant increase in brain cortex beta-APP expression, increased tau phosphorylation, and a marked relative expansion of the trans- part of the Golgi intracellular secretory pathway in cortical neurons has been found. The changes of beta-APP expression and tau phosphorylation appeared within 1 h after 2-DG application and continued for at least 24 h. However, brain 31P resonance spectra remained unchanged for up to 7.5 h after 2-DG. It is suggested that the increase of beta-APP expression represents a response of brain tissues to 2-DG-evoked biochemical stress, while tau hyperphosphorylation and the change in Golgi morphology may be secondary phenomena.

[Nucleoside analogs in the treatment of primary malignant brain tumors]. / Pochodne nukleozydowe w leczeniu pierwotnych zlosliwych nowotworów mózgu.

Standard therapeutic modalities including surgery, radio- and/or peripheral chemotherapy are ineffective in malignant gliomas. This is due to infiltration of distant brain areas by glioma cells and to the blood-brain barrier limiting penetration of anticancer drugs. One of the most promising experimental methods of glioma therapy is intracerebral implantation of biodegradable polymers containing cytotoxic compounds. This method allows to avoid peripheral toxicity of drugs. Considering that practically it is only malignant cells that proliferate in the brain, the use of drugs displaying selective toxicity toward DNA-replicating cells might help to avoid central toxicity as well. Several nucleoside analogs display selective cytotoxic and/or radiosensitizing effects on proliferating cells. Despite encouraging results obtained in the in vitro and animal models of gliomas, peripheral administration of these drugs turned out to be ineffective in the clinical settings. Intracerebral implantation of nucleoside analogs-containing biodegradable polymers may be much more efficacious, especially when combined with radiotherapy. Appropriate nucleoside analogs may also be employed in cell-selective radiotherapy and gene therapy of malignant gliomas.

Impact of donor health on corneal biochemistry--an unexpected caveat from a pilot study.

BACKGROUND: To test the possibility that some chronic systemic maladies not directly related to the function of the eye may significantly and permanently disturb corneal metabolism. MATERIAL/METHODS: Contents of selected low molecular weight metabolites were compared among corneas collected from donors who died suddenly of an accident or non-poisoning suicide, or met a sudden non-accidental death from unidentified causes, or died of a chronic cardiovascular disease or of idiopathic liver cirrhosis (N=4 for each group). Corneal buttons were halved; one half was snap-frozen and stored at -80°C, and the other half was stored at +4°C in Eusol-C for 8 days and then was snap-frozen and stored at -80°C until analyzed. Metabolite contents were assessed using high-resolution magic angle spinning proton NMR spectroscopy. RESULTS: Significant between-group differences in corneal biochemical profiles were identified. Most of them were reduced or nullified by the Eusol-C storage, suggesting their link to differences in in vivo corneal environment. The corneas from donors with liver cirrhosis or cardiovascular diseases differed considerably from the remaining ones, both before and after the Eusol-C storage. CONCLUSIONS: Various chronic systemic diseases that are not directly related to the function of the eye markedly affect corneal biochemistry. Some of the alterations are likely related to a permanent aberration in corneal metabolism. A study is warranted in larger donor groups on the effect of idiopathic liver cirrhosis and cardiovascular diseases on corneal metabolism and/or a retrospective analysis of the long-term outcome of keratoplasty and other grafting procedures employing materials from these donor groups.