Periodontitis, Blood Pressure, and the Risk and Control of Arterial Hypertension: Epidemiological, Clinical, and Pathophysiological Aspects-Review of the Literature and Clinical Trials.

PURPOSE OF REVIEW: Arterial hypertension is an important risk factor for cardiovascular disease. In the world, about 45% of people suffer from arterial hypertension, while good blood pressure control is achieved by only approximately 50% of all hypertensive patients treated. The reason for the high prevalence of arterial hypertension and its poor control is low knowledge of hypertensinogenic factors. One such factor is periodontitis, which is a disease of social importance. RECENT FINDINGS: It has been shown that the occurrence of periodontitis leads to an increase in blood pressure, increasing the risk of arterial hypertension. Periodontitis can also lead to ineffectiveness of antihypertensive treatment. Some interventional studies have shown that treatment of periodontitis reduced blood pressure in patients with arterial hypertension. The pathogenesis of arterial hypertension in periodontitis is complex and concerns mainly the impairment of the vasodilatation properties of the endothelium. Hygiene and periodontitis treatment should be a method of preventing arterial hypertension and a method of increasing the effectiveness of antihypertensive treatment.

Natriuretic peptides in diagnostics and therapy.

Natriuretic peptides are peptide hormones which are involved in the regulation of blood pressure, water-mineral balance and multiple metabolic processes. The beginning of research on this group of hormones starts in 1981, when the deBold and collaborators discovered ANP. Eight natriuretic peptides have been described so far: ANP, BNP, CNP, DNP, urodilatin, uroguanylin, osteocrin, musculin and three receptors: NPR-A, NPR-B and NPR-C thanks to which these hormones accomplish their physiological functions. Determination of natriuretic peptide concentration in plasma is used in the diagnosis and treatment of heart failure and pulmonary embolism. Research results indicate that the determination of natriuretic peptides concentration in plasma may also be important in the acute coronary syndromes, subclinical complications of hypertension and atrial fibrillation. The concentration of natriuretic peptides is changing in many diseases. The beneficial effects of natriuretic peptides have led to the production of drugs that are their synthetic derivatives. These drugs are mainly used among patients with heart failure. Research is currently underway on the efficacy and safety of other synthetic natriuretic peptides.

Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths.

Arterial hypertension is the most common comorbid disease in patients who died as a result of SARS-Cov-2 infection. Numerous observational studies indicate a relationship between arterial hypertension and its treatment and SARS-Cov-2 coronavirus infection. It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell. There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection. It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell. Blood glucose as well as lipid profile should be monitored during SARS-Cov-2 coronavirus infection. This article attempts to gather key information on arterial hypertension and COVID-19.

[The impact of electronic cigarettes usage on the endothelial function and the progression of atherosclerosis]. / Wplyw uzywania papierosów elektronicznych na funkcje sródblonka naczyniowego oraz rozwój miazdzycy.

The exponetial growth in popularity of electronic cigarettes in the world markets intensifies the debate about their health effects. The smoking of traditional tabacoo products is a factor associated with the endothelium damage and progression of atherosclerosis. The elimination of the combustion process in electronic cigarettes allows to conclude that they are less harmful to a vascular endothelium than traditional tobacco products. E-cigarette aerosol contains many compounds that have an influence on initiation and progression of atherosclerosis. Nicotine protherogenic action is not fully explained. On one hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas epidemiological studies do not show an increased risk of cardiovascular disease in the population using nicotine replacement therapy or snuff. Acrolein, formaldehyde and the ultrafine particles generated during e-liquid heating have an impact on initiation and progression of atherosclerosis, but their level is lower than that of tobacco smoke. In order to assess accurately the longterm effects of e-cigarettes, it is necessary to conduct epidemiological studies measuring the effects of using e-cigarettes. It is claimed that the use of electronic cigarettes has a potential impact on the development of atherosclerosis, but is significantly lower than that of traditional cigarettes.

Untargeted Plasma Metabolomics Identifies Endogenous Metabolite with Drug-like Properties in Chronic Animal Model of Multiple Sclerosis.

We performed untargeted metabolomics in plasma of B6 mice with experimental autoimmune encephalitis (EAE) at the chronic phase of the disease in search of an altered metabolic pathway(s). Of 324 metabolites measured, 100 metabolites that mapped to various pathways (mainly lipids) linked to mitochondrial function, inflammation, and membrane stability were observed to be significantly altered between EAE and control (p < 0.05, false discovery rate <0.10). Bioinformatics analysis revealed six metabolic pathways being impacted and altered in EAE, including α-linolenic acid and linoleic acid metabolism (PUFA). The metabolites of PUFAs, including ω-3 and ω-6 fatty acids, are commonly decreased in mouse models of multiple sclerosis (MS) and in patients with MS. Daily oral administration of resolvin D1, a downstream metabolite of ω-3, decreased disease progression by suppressing autoreactive T cells and inducing an M2 phenotype of monocytes/macrophages and resident brain microglial cells. This study provides a proof of principle for the application of metabolomics to identify an endogenous metabolite(s) possessing drug-like properties, which is assessed for therapy in preclinical mouse models of MS.

[Astrocytes in ischemic stroke - a potential target for neuroprotective strategies]. / Astrocyty w udarze niedokrwiennym mózgu ­ potencjalny cel strategii neuroprotekcyjnych.

Ischemic stroke is one of the leading causes of adult death and disability worldwide. Present applied therapeutic strategies do not give satisfactory results. It is often emphasized that pharmacological actions aimed at reducing the area of ischemic brain injury should protect astrocytes forming together with neurons and the endothelium neurovascular unit. Astrocytes contribute importantly to proper neuronal function during both physiological and pathological conditions. In ischemic stroke, astrocytes are involved in regulation of water and ion homeostasis, cerebral blood flow, maintenance of the blood-brain barrier, and control of the extracellular level of glutamate, as well as being a source of neuroprotectants. On the other hand, astrocytes may also contribute to enlarged ischemic area due to their participation in inflammatory processes and production of potential neurotoxic substances. Herein we review experimental and clinical data concerning adaptive and pathological roles of astrocytes during both early and late phases of ischemia. Especially, we emphasize specific features of astrocytes that might become a potential target of therapeutic strategies for ischemic stroke.

[Fecal transplantation the future therapy?]. / Transplantacja stolca terapia przyszlosci?

Intestinal bacteria play an important role in human physiology, taking part in the metabolism, absorption of nutrients and regulation of the immune system. In many illnesses the bacterial imbalance in the digestive tract occurs, and fecal transplantation is one method that allows you to restore the balance. The essence of the described method is to replace the pathogenesis, abnormal bacterial flora with the flora occurring in normal healthy individuals. So far, the main use of the method described in the article is resistant to antibiotics Clostridium difficile infection, which gives you a chance to avoid total colectomy. The article presents an accurate description of the same procedure to prepare the material, the selection of donor, recipient preparation and diseases, such as inflammatory bowel diseases, irritable bowel syndrome, diabetes and obesity, in which this method of treatment is currently practised.

[Oncolytic viruses as a new way of treatment of neoplastic diseases]. / Wirusy onkolityczne najnowszym sposobem walki z chorobami nowotworowymi.

Despite the unceasing progression in chemotherapy, radiotherapy and surgery, neoplasms are still the second, after cardiovascular diseases, cause of death in the world. The creation of oncolytic viruses gives hope for increase of anticancer therapy effectiveness. Oncolytic viruses are the type of viruses that selectively infect and cause the lyse of tumor cells excluding normal cells. This mechanism allows to avoid the consequences of the possible replication of the virus, which having entered to the organism, replicates in organism's cells by using the DNA of host cells. The development of genetic engineering and molecular biology has enabled the creation of this kind of genetically modified viruses, which deprive them of their virulence. Currently, there are many clinical trials in progress including the use of oncolytic viruses in head and neck squamous cell carcinoma, thyroid cancer, colorectal cancer, liver cancer, melanoma and glioblastoma multiforme treatment. There are parallel studies in animals using the subsequent viruses. Oncolytic viruses treatment is generally well tolerated, without significant side effects. It is worth to point out that this method combined with chemotherapy and radiotherapy allows to reduce the use of therapeutic doses, which significantly reduces the toxicity of conventional treatment. Further clinical studies evaluating the efficacy and safety of oncolytic viruses will develop more effective and better tolerated therapeutic protocols in the future.

[Mental disorders in digestive system diseases - internist's and psychiatrist's insight]. / Zaburzenia psychiczne w chorobach przewodu pokarmowego - spojrzenie internisty i psychiatry.

Mental disorders accompanying digestive system diseases constitute interdisciplinary yet scarcely acknowledged both diagnostic and therapeutic problem. One of the mostly recognized examples is coeliac disease where patients endure the large spectrum of psychopathological symptoms, starting with attention deficit all the way down to the intellectual disability in extreme cases. It has not been fully explained how the pathomechanism of digestive system diseases affects patient's mental health, however one of the hypothesis suggests that it is due to serotonergic or opioid neurotransmission imbalance caused by gluten and gluten metabolites effect on central nervous system. Behavioral changes can also be invoked by liver or pancreatic diseases, which causes life-threatening abnormalities within a brain. It occurs that these abnormalities reflexively exacerbate the symptoms of primary somatic disease and aggravate its course, which worsens prognosis. The dominant mental disease mentioned in this article is depression which because of its effect on a hypothalamuspituitary- adrenal axis and on an autonomic nervous system, not only aggravates the symptoms of inflammatory bowel diseases but may accelerate their onset in genetically predisposed patients. Depression is known to negatively affects patients' ability to function in a society and a quality of their lives. Moreover, as far as children are concerned, the occurrence of digestive system diseases accompanied by mental disorders, may adversely affect their further physical and psychological development, which merely results in worse school performance. All those aspects of mental disorders indicate the desirability of the psychological care for patients with recognized digestive system disease. The psychological assistance should be provided immediately after diagnosis of a primary disease and be continued throughout the whole course of treatment.

[Novel strategies of ovarian cancer treatment]. / Nowe strategie leczenia raka jajnika.

Ovarian cancer is the most lethal gynecological malignancy. Due to scarce specific symptoms, women usually seek medical help once the disease is highly advanced, with distant metastases. Currently no screening is available, making this particular cancer hard to detect in the early stage. Standard treatment is insufficient for many patients, especially in the recurrent disease. This fact explains the tremendous need to search for novel therapeutic approaches. Inhibition of angiogenesis and destruction of cancer stem cells are attempts that affect the tumor microenvironment. There is a lot of potential in inhibiting poly(ADP-rybose)polymerase (PARP) or I class histone deacetylase. Drug repositioning may also be beneficial, as it gives old drugs new purposes. Metformin, a well-known antidiabetic agent, is an example of this phenomenon. Constant progress in medicine and science makes us hope for positive outcomes while treating this highly dangerous disease.

[Antiangiogenic therapy of malignant pheochromocytoma and paraganglioma with the view to the recent scientific developments]. / Antyangiogenna terapia zLoSliwej postaci pheochromocytoma i paraganglioma w Swietle najnowszych doniesieN naukowych.

Pheochromocytoma is a very rare tumor that stems from chromaffin cells and usually develops in the adrenal glands. Its equivalent, which exists outside of the adrenal glands, is paraganglioma. Approximately 10-26% of pheochromocytoma is malignant, what poses a significant therapeutical problem, as its presence, together with an abundant production of catecholamines, may lead to a number of perilous complications, such as spinal cord oppression or the damage of organs, what is responsible for producing catecholamines. Due to the risk that the tumor is, it is essential to event new and effective ways of treatment. In case of malignant tumors stemming from chromaffin cells, much is expected from antiangiogenic medicine. Its functioning consists of stopping of the process of neovascularization, which is indispensable for the development of the tumor. Sunitinib - a tyrosine kinase inhibitor - is perhaps the most promising antiangiogenic medicine, whose effectiveness is currently being evaluated in 2nd phase clinical trials. Attempts are also being made to conduct treatment with the use of other medicine of similar functioning, such as: thalidomide, imatinib or evrolimus.

AMP-activated protein kinase is involved in induction of protective autophagy in astrocytes exposed to oxygen-glucose deprivation.

AMP-activated kinase (AMPK) acts as the intracellular ATP depletion sensor, which detects and limits increases in the AMP/ATP ratio. AMPK may be significantly activated under stress conditions that deplete cellular ATP levels such as ischemia/hypoxia or glucose deprivation. Recent studies strongly suggest that AMPK participates in autophagy regulation, but it is not known whether AMPK activated by ischemia regulates autophagy in astrocytes and the consequence of autophagy activation in ischemic astrocytes are unclear. We have investigated the contribution of AMPK to autophagy activation in rat primary astrocyte cultures subjected to ischemia-simulating conditions (combined oxygen glucose deprivation, OGD) and its potential effects on astrocyte damage induced by OGD (1-12 h). The evidence supports the conclusion that AMPK activation at early stages of OGD is involved in induction of protective autophagy in astrocytes. Inhibition of AMPK, either by siAMPKα1 or by compound C, significantly attenuated the expression of autophagy-related proteins and decrease of astrocyte viability following OGD. The findings provide additional data about the role of AMPK in ischemic astrocytes and downstream responses that may be involved in OGD-induced protective autophagy.

A peptide nucleic acid (PNA)-mediated polymerase chain reaction clamping allows the selective inhibition of the ERVWE1 gene amplification.

A new peptide nucleic acid (PNA) mediated QPCR technique for the detection and quantification of the Multiple Sclerosis-Associated Retrovirus (MSRV) belonging to the human endogenous retrovirus-W (HERV-W) family has been developed. The assay utilizes a PNA probe which is fully complementary to the ERVWE1 sequence, another member of the HERV-W family which is closely related to MSRV. Due to its excellent affinity to a completely matched template, PNA probe selectively blocks the amplification of ERVWE1 thus allowing the specific and exclusive detection and quantification of the MSRV as PNA does not interfere with the amplification of MSRV. Using this newly developed method we found that MSRV is predominantly expressed over ERWVE1 in astrocyte-derived U-87 MG cell line but not in human umbilical vein endothelial cells or human placental cells.

[Metformin as a key to alternative activation of microglia?]. / Metformina kluczem do alternatywnej aktywacji mikrogleju?

The results of recent studies suggest that metformin, in addition to its antihyperglycemic efficacy, may also attenuate neuroinflammation and directly act on the central nervous system. However, the molecular mechanisms by which metformin exerts its anti-inflammatory effects in the brain remain largely unknown. Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action. However, some of the biological responses to metformin (e.g. the release of cytokines and the expression of arginase I or PGC-1α) are not limited to AMPK activation but also are mediated by AMPK-independent mechanisms. This article reviews current evidence supporting the hypothesis that the shift of microglia toward alternative activation may underlie the beneficial effects of metformin observed in animal models of neurological disorders.

[Dysregulation of the mTOR signaling pathway in the pathogenesis of autism spectrum disorders]. / Dysregulacja szlaku sygnalowego mTOR w patogenezie zaburzen ze spektrum autystycznego.

Mammalian target of rapamycin (mTor) plays multiple role in central nervous system and is involved in regulation of cell viability, differentiation, transcription, translation, protein degradation, actin cytoskeletal organization and autophagy. Recent experimental and clinical studies reveal that disturbances of mTOR signaling are involved in the pathogenesis of autism spectrum disorders (ASD). This article reviews current data on the alteration in the mTOR transduction cascade, which may contribute to common neurobehavioral disorders typical for ASD. Moreover, the results of the latest experimental studies on the potential of mTOR inhibitors for the treatment of ASD are reviewed.

[The newest perspectives on the treatment of glioblastoma multiforme]. / Najnowsze perspektywy w leczeniu glejaka wielopostaciowego.

Glioblastoma multiforme is the most common and most malignant primary brain tumor, with a yearly incidence of 2.5 in 100,000. It has a very dismal prognosis, since the medium overall survival of untreated patients is as low as 3 months. Location in the central nervous system, high aggressiveness, spreading alongside blood vessels and white matter, cause a lot of therapeutic challenges. The blood-brain barrier unables most of the systemic drugs to reach the tumor and complete resection is usually impossible. Because of that, effects of the standard treatment remain unsatisfying. It forces to search for novel treatment options. Regarding pharmacotherapy a lot of attention is brought to antiangiogenic therapies, where the most common drug is bevacizumab. In Europe it is registered to use in diffuse breast cancer, non-small cell lung cancer, colon and rectal cancer with metastases, but for glioblastoma it's use is still considered to be experimental. Inhibition of integrins, extracellular matrix metalloproteinases and EGFR are among other therapeutic goals. There is a broad range of studies on breaking the resistance of cancer stem cells, modifying the niche of cancer cells, active immunotherapy and the use of microRNAs. The field of stereotactic radiosurgery is also under constant improvement. Methods of both genetic and biomedical engineering, such as nanotubes or liposomes, can be helpful to overcome the blood-brain barrier and insert the drugs directly and even selectively into the tumor.

[Drugs malabsorption after bariatric surgery]. / Zaburzenia wchlaniania leków u chorych po operacjach bariatrycznych.

Along with the increasing prevalence of obesity surgical methods of treatment are becoming more accessible. The success of bariatric surgery results from the failure of conservative treatment of obesity through diet, exercises and behavioral changes. Such behaviors, including less effective drug therapy, are responsible for rather small and unstable weight reduction. In contrast, surgical treatment restrictions limiting the amount of food intake, excluding treatments and mixed treatments usually give a spectacular effect, though it is not always consistent with the previous assumptions. Most of us, however, do not realize the risk of the consequences that these treatments bring. The change of the absorption of oral medications, vitamins, microelements, often change the way they are metabolized and it forces ones to change the form of the drug, the way they are taken, which undoubtedly is associated with higher costs of later treatment. Many clinicians are unaware of the need for lifelong supplementation of some vitamins and microelements, as well as the need to modify pharmacotherapy in patients who have undergone this type of operations. This article presents examples of the best known and described changes in the absorption of drugs and micronutrients and explains how well oriented the internist ought to be when qualifying a patient to undergo this type of treatment. The described topic is interesting, but also controversial due to the fact that it corresponds closely with the surgical specialties, quite spectacular in their effects and behavioral specializations, that in many years time will be looking after the patient who underwent the surgery, but is still sick.

[Actual diagnosis, treatment and prevention of human granulocytic anaplasmosis]. / Aktualne postqpowanie diagnostyczne, terapeutyczne i prewencyjne w ludzkiej anaplazmozie granulocytarnej.

Ixodes ricinus tick is widely known as a reservoir and vector for many dangerous pathogens. One of them is gram-negative bacteria called Anaplasma phagocytophilum, that may cause human granulocytic anaplasmosis (formerly called granulocytic ehrlichiosis). Development of modem diagnostics, which allows the implementation of effective pharmacotherapy, caused that this disease can be effectively detected only for last couple years. Human granulocytic anaplasmosis in most cases is not a severe ailment, but in some patients, especially improperly diagnosed and treated, it can lead to serious complications or even death. Due to non-specific clinical symptoms and a small number of laboratories proceeding specialized tests, human granulocytic anaplasmosis constitutes clinical and diagnostic problem. A significant increase in tick-borne diseases needs to increase public and physicians awareness of these issues.

[Hyperthermic intraperitoneal chemotherapy as a new way of peritoneal metastases treatment]. / Dootrzewnowa chemioterapia perfuzyjna w hipertermii jako nowy sposób leczenia przerzutów nowotworowych do otrzewnej.

Peritoneal neoplastic disease may originate primarily from neoplasms developing in peritoneum or metastases of cancers mostly arising in digestive or female reproductive systems. Peritoneal neoplasia leads to a much poorer prognosis and in most cases the palliative care, which focus on gastrointestinal motility and patency, adequate analgesia and psychological care, is being introduced. Systemic chemotherapy is ineffective as a result of existence of physiological blood-peritoneal barrier that blocks hydrophilic chemotherapeutics. Nowadays there are attempts to eliminate this problem by performing cytoreductive surgery accompanied by hyperthermic intraperitoneal chemotherapy (HIPEC). Undoubtedly the possibility to gain high local concentration of chemotherapeutic directly in peritoneal cavity is primary advantage of this method. In the carried out clinical trials the efficiency of this procedure in prolonging patient life in a relatively good comfort was proven. This method is highly recommended in case of peritoneal metastases from colorectal cancer treatment. There are ongoing studies focused on proving the effectiveness of HIPEC in case of other types of neoplasms and use of that therapy as a prophylactic treatment before metastases occur.

[Ocular symptoms in rheumatic diseases]. / Objawy oczne w wybranych chorobach reumatycznych.

Rheumatic diseases are frequently associated with eye disorders presenting with a wide range of signs and symptoms. Dry eye syndrome, keratitis, uveitis, scleritis and retinal vasculitis are often diagnosed in patients with rheumatic diseases. It is important not to overlook even subtle signs of ocular involvement as it may result in serious complications. Moreover in some cases ocular manifestation may help in proper diagnosis of systemic condition or indicate necessity of intensified treatment of underlying condition. Appropriate treatment of rheumatic diseases require careful follow up and involvement of various specialists including ophthalmologists as well as patient education.