Ryszard Rutkowski

Dehydroepiandrosterone (dhea): Hypes and Hopes

Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. In animal studies, their low levels have been associated with age-related involuntary changes, including reduced lifespan. Extrapolation of animal data to humans turned DHEA into a ‘superhormone’ and an ‘anti-aging’ panacea. It has been aggressively marketed and sold in large quantities as a dietary supplement. Recent double-blind, placebo-controlled human studies provided evidence to support some of these claims. In the elderly, DHEA exerts an immunomodulatory action, increasing the number of monocytes, T cells expressing T-cell receptor gamma/delta (TCRγδ) and natural killer (NK) cells. It improves physical and psychological well-being, muscle strength and bone density, and reduces body fat and age-related skin atrophy stimulating procollagen/sebum production. In adrenal insufficiency, DHEA restores DHEA/DHEAS and androstenedione levels, reduces total cholesterol, improves well-being, sexual satisfaction and insulin sensitivity, and prevents loss of bone mineral density. Normal levels of CD4+CD25hi and FoxP3 (forkhead box P3) are restored. In systemic lupus erythematosus, DHEA is steroid-sparing. In an unblinded study, it induced remission in the majority of patients with inflammatory bowel disease. DHEA modulates cardiovascular signalling pathways and exerts an anti-inflammatory, vasorelaxant and anti-remodelling effect. Its low levels correlate with increased cardiovascular disease and all-cause mortality. DHEA/DHEAS appear protective in asthma and allergy. It attenuates T helper 2 allergic inflammation, and reduces eosinophilia and airway hyperreactivity. Low levels of DHEAS accompany adrenal suppression. It could be used to screen for the side effects of steroids. In women, DHEA improves sexual satisfaction, fertility and age-related vaginal atrophy. Many factors are responsible for the inconsistent/negative results of some studies. Overreliance on animal models (DHEA is essentially a human molecule), different dosing protocols with non-pharmacological doses often unachievable in humans, rapid metabolism of DHEA, co-morbidities and organ-specific differences render data interpretation difficult. Nevertheless, a growing body of evidence supports the notion that DHEA is not just an overrated dietary supplement but a useful drug for some, but not all, human diseases. Large-scale randomised controlled trials are needed to fine-tune the indications and optimal dosing protocols before DHEA enters routine clinical practice.

Allergic diseases: the price of civilisational progress

Atopic disorders are a major global health problem. The prevalence of asthma, allergic rhinitis and atopic dermatitis has been increasing over the last four decades, both in the industrialized and developing countries. It seems to be related to changes in the social structure, increasing industrialization, pollution and dietary changes. Many hypotheses link the allergy epidemic to stringent hygiene, dominance of a westernized lifestyle and an accelerated pace of life. Dietary antioxidants, lipids, sodium, vitamin D seem also to be implicated. We endeavour to review the most relevant theories with a special emphasis on the hygiene, antioxidative, lipid and air pollution hypotheses. It is however important to note that none of them explains all the aspects of unprecedented rise in the prevalence of allergic disorders. A complex interplay between hosts immune response, invading pathogens, diversity of environmental factors and genetic background seems to be of a particular importance. Current allergy epidemic is multifactorial and basic and epidemiologic studies are warranted to further our understanding of this phenomenon.

Activity of lysosomal exoglycosidases in serum and synovial fluid in patients with chronic Lyme and rheumatoid arthritis

Lysosomal exoglycosidases participate in the destruction of the articular cartilage by cleaving glycoside bonds in glycoproteins and proteoglycans. The aim of the study was to determine the activity of exoglycosidases: hexosaminidase, β-glucuronidase, β-galactosidase, α-mannosidase and α-fucosidase in serum and synovial fluid of patients with Lyme and rheumatoid arthritis. The study group consisted of 10 patients with chronic Lyme arthritis (age 18 – 74 y), 13 with rheumatoid arthritis (age 32 – 70 y) and 10 with juvenile idiopathic arthritis (age 8 – 17 y). The control group consisted of 9 healthy volunteers (age 24 – 62 y). The activity of the exoglycosidases was determined with the p-nitrophenyl derivatives of sugars as substrates. A significant increase of the activity of all the exoglycosidases in serum and in synovial fluid of the patients with different forms of arthritis was found. The ratio of synovial fluid/serum activity of exoglycosidases was above 2.0 in LA but not in JIA and RA patients. As the main source of exoglycosidases in the joint is the synovial membrane, this result supports the appropriateness of therapeutic synovectomy in chronic Lyme arthritis with knee effusion. The serum activity of hexosaminidase may be used in monitoring the course of Lyme arthritis and the efficiency of treatment.

Aberrant Distributions and Relationships Among E-cadherin, β-catenin, and Connexin 26 and 43 in Endometrioid Adenocarcinomas

During carcinogenesis, loss of intracellular cohesion is observed among cancer cells with altered expression of such adhesion molecules as E-cadherin and β-catenin, and aberrant expression and cellular location of intercellular gap junction proteins-connexins. The aim of this study was to evaluate immunohistochemically the expression and relationship between E-cadherin and β-catenin, and the connexins Cx26 and Cx43 in 86 endometrioid adenocarcinomas. The aberrant cytoplasmic translocation of the studied proteins was a predominant finding, whereas only a minority of cases showed normal, nuclear β-catenin labeling or membranous distribution of the remaining molecules. E-cadherin was positively and significantly associated with β-catenin (P=0.001, r=0.366), as was Cx26 with Cx43 (P<0.001, r=0.719), E-cadherin with Cx26 (P<0.001, r=0.413), and E-cadherin and Cx43 (P<0.001, r=0.434) in all cancers. A subgroup of endometrioid adenocarcinomas (FIGO IB+II) exclusively showed a positive significant association between the expression of β-catenin and Cx26 (P=0.038, r=0.339). In addition, there were significantly more β-catenin-positive carcinomas among superficially spreading cancers (FIGO IA) than among deeper invading neoplasms (FIGO IB+II) (P=0.056). The altered location of the studied proteins indicates impairment of their physiological functions. In particular, normal membranous distribution of E-cadherin and connexins is lost and replaced by abnormal cytoplasmic accumulation in most cancers, and thus intercellular ties are expected to be weakened and loosened as a consequence. In contrast, the lack of relationship between β-catenin and connexins, E-cadherin seems to be closely associated with the expression of Cx26 and Cx43 in endometrioid adenocarcinomas.

Optical radiation in modern medicine

Optical radiation extends between microwaves and X-rays of the electromagnetic radiation and includes ultraviolet (UV), visible light (VL) and infrared (IR) components. The dose of radiation that reaches the skin is influenced by the ozone layer, position of the Sun, latitude, altitude, cloud cover and ground reflections. The photobiological effects of UV, VL and IR bands depend on their wavelength, frequency and mechanism of action. They are modified by the thickness, structure, vasculature and pigmentation of skins stratum corneum, epidermis and dermis. Following absorption, IR affects the body mainly through transfer of thermal energy to tissues. Visible light and skin interact either thermally or photochemically, whereas UV acts mainly photochemically. Optical radiation in the form of sunlight therapy had been used already in ancient times. Nowadays IR, VL and UV are widely applied in the therapy of allergic, dermatological, cardiovascular, respiratory, rheumatic, neonatal, pediatric and psychiatric disorders.

Evaluation of NF-κB concentration in patients with tick-borne encephalitis, neuroborreliosis, anaplasmosis and Anaplasma phagocythophilum with tick-borne encephalitis virus co-infection

Objectives The aim of the study was the evaluation of NF‐&kgr;B concentration in serum and cerebrospinal fluid (CSF) of patients with diagnosis of tick‐borne diseases: tick‐borne encephalitis (TBE), neuroborreliosis (NB), anaplasmosis (ANA) and patients co‐infected with tick‐borne encephalitis virus and Anaplasma phagocythophilum (TBE + ANA). Additionally NF‐&kgr;B concentration during acute and convalescent period was compared. Methods Sixty‐seven patients with diagnosis of tick‐borne diseases were included in the study. The control group (CG) consisted of 18 patients hospitalized because of headaches and had lumbar puncture performed. The NF‐&kgr;B was measured by human inhibitory subunit of NF‐&kgr;B ELISA Kit during acute and convalescent period. Results In serum the significant differences were observed only in patients with TBE + ANA co‐infection. In CSF the concentration of NF‐&kgr;B was significantly higher in patients with TBE, TBE + ANA co‐infection, and patients with NB than in CG. Receiver operating characteristic (ROC) curves analysis showed that NF‐&kgr;B concentration in CSF differentiated patients with NB with CG; patients co‐infected with TBE and ANA with CG and patients with TBE with CG. NF‐&kgr;B concentration in serum differentiated patients co‐infected with TBE and ANA with NB and with ANA, with TBE and with CG. In TBE group the serum NF‐&kgr;B concentration significantly decreased in convalescent period, while in NB and TBE groups significant CSF decrease of NF‐&kgr;B concentration was observed. ConclusionsInflammatory process in the CNS results in the increase of NF‐&kgr;B concentration in CSF, due to the damage of blood‐brain barrier.Co‐infection of TBE + ANA increases NF‐&kgr;B concentration in serum.NF‐&kgr;B concentration in serum may be useful in the differentiation of TBE + ANA co‐infection with TBE and NB.NF‐&kgr;B concentration may be used to monitor TBE and NB treatment effectiveness. HighlightsNF‐&kgr;B increases in cerebrospinal fluid (CSF) during nervous system inflammation.Tick‐borne encephalitis with anaplasmosis (TBE + ANA) increases NF‐&kgr;B in serum.Serum NF‐&kgr;B concentration differentiates TBE + ANA with TBE and neuroborreliosis.Serum and CSF NF‐&kgr;B concentration may monitor tick‐borne encephalitis treatment.Cerebrospinal fluid NF‐&kgr;B concentration may monitor neuroborreliosis treatment.

Meningitis, Clinical Presentation of Tetanus

Background. Tetanus is an acute disease caused by a neurotoxin produced by Clostridium tetani. Tetanus immunization has been available since the late 1930s but sporadic cases still occur, usually in incompletely vaccinated or unvaccinated individuals. Case Report. An elderly previously vaccinated female contracted tetanus following foot injury. Clinically she presented with meningitis causing diagnostic and therapeutic delays. Why Should Physician Be Aware of This? Even in developed countries the differential diagnosis of meningitis, especially in the elderly, should include tetanus. Treatment in intensive care unit is required. General population might benefit from vaccine boosters and education on this potentially fatal disease.