Statiinid ja ateroskleroos

Et südame-veresoonkonnahaigused (SVH) on juhtiv surmapõhjus USAs ja Euroopas, pööratakse modifitseeritavate riskitegurite (eeskätt arteriaalse hüpertensiooni ja düslipideemia) mõjutamisele palju tähelepanu. Kliiniliselt enim kasutatud ravimirühmaks lipiidide mõjustamisel on vaieldamatult 3-hüdroksü-3-metüülglutarüül-koensüüm A reduktaasi inhibiitorid ehk statiinid, mis võlgnevad oma ainulaadse koha düslipideemiate farmakoteraapias peamiselt jõulisele LDL-kolesterooli sisaldust alandavale toimele. Statiinid vähendavad relatiivset riski SVH tekkes 24–37% ja nende prognoosi parandav toime ei sõltu uuritavate vanusest, soost, südame isheemiatõve või teiste kaasuvate haiguste olemasolust (1). Riigiti on statiinide kasutamine väga erinev. Kuigi Eestis on suremus SVHsse Euroopa suuremaid, kasutatakse meil statiine sekundaarses profülaktikas umbes 10 korda vähem kui Põhjamaades (2, 3) (vt jn 1). Eesti Arst 2007; 86 (3): 157–16

ST-elevatsiooniga äge südameinfarkt ägeda peritoniidiga patsiendil

Artiklis on kirjeldatud ühe haigusjuhu diagnostikat ja ravitaktikat alates vastuvõtuosakonnast kuni koju kirjutamiseni. Patsiendil esines ühel ajal kaks rasket haigusseisundit: ägeda ST-elevatsiooniga müokardiinfarkt ja ägeda peritoniidiga kulgev duodenum’i perforatsioon. Kuna patsient oli šokis ja hemodünaamiliselt ebastabiilne, tehti haigele kõigepealt koronarograafia ja revaskulariseerimine ning stabiliseeriti hemodünaamika. Pärast edukat revaskulariseerivat ravi tehti patsiendile mao resektsioon ja duodeenumi köndi dekomprimeeriv drenaažkomplitseeritud duodenaalhaavandi perforatsiooni tõttu. Patsient kirjutati kirurgiakliinikust koju 26. ravipäeval paranenuna. Eesti Arst 2012; 91(6):311–31

Oomega-3 rasvhapped vähendavad märkimisväärselt seerumi triglütseriidisisaldust düslipideemiaga patsientidel

Hüpertriglütserideemiat peetakse südame-veresoonkonnahaiguste iseseisvaks riskiteguriks, kusjuures triglütseriidisisalduse suurenemine veres 1 mmol/l suurendab kardiovaskulaarse haigestumise riski meestel 30% ning naistel isegi kuni 76%. Uuringud kalast ja kalaõlist toodetud oomega-3 rasvhapete mõjust tõestavad nende kaitsvat toimet aterosklerootilise südamehaiguse ning koronaarse äkksurma vastu. Uurimuse eesmärgiks oli hinnata 1,2 grammi oomega-3 rasvhapete toimet seerumi triglütseriidisisaldusele hüpertriglütserideemiaga patsientidel, kellel dieedisoovitustele vaatamata ei olnud seerumi triglütseriidisisaldus normaliseerunud ning kes ei saanud statiinravi. Eesti Arst 2005; 84 (11): 771–77

Hüperkolesteroleemia kombineeritud ravi statiinide ja esetimiibiga

Paljude epidemioloogiliste uuringutega on tõestatud, et suur vere kolesteroolisisaldus on üheks koronaartõve riskiteguriks. Vaatamata sellele ei ole piisavalt igapäeva praktikasse juurdunud vere kolesteroolitaseme mõõtmine ja selle ravimitega mõjustamine ei südamehaiguste riskirühma kuuluvatel ega koronaartõvega patsientidel. Eesti Arst 2005; 84 (1): 47-4

T-helper Cell-Mediated Proliferation and Cytokine Responses against Recombinant Merkel Cell Polyomavirus-Like Particles

The newly discovered Merkel Cell Polyomavirus (MCPyV) resides in approximately 80% of Merkel cell carcinomas (MCC). Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT) viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL), suggesting a pathogenic role also in CLL. About 50–80% of adults display MCPyVspecific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC) of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs), using human bocavirus (HBoV) VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-c, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyVseropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-c. The MCPyV antigen tended to induce stronger IFN-c responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-c responses. IFN-c being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance.Peer reviewe

Eesti perekondliku hüperkolesteroleemia käsitlusjuhend

Eesti Arst 2023; 102(4):237–24

Serodiagnosis of Primary Infections with Human Parvovirus 4, Finland

To determine the prevalence of parvovirus 4 infection and its clinical and sociodemographic correlations in Finland, we used virus-like particle–based serodiagnostic procedures (immunoglobulin [Ig] G, IgM, and IgG avidity) and PCR. We found 2 persons with parvovirus 4 primary infection who had mild or asymptomatic clinical features among hepatitis C virus–infected injection drug users

A 10-Minute “Mix and Read” Antibody Assay for SARS-CoV-2

Accurate and rapid diagnostic tools are needed for management of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Antibody tests enable detection of individuals past the initial phase of infection and help examine vaccine responses. The major targets of human antibody response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the spike glycoprotein (SP) and nucleocapsid protein (NP). We have developed a rapid homogenous approach for antibody detection termed LFRET (protein L-based time-resolved Förster resonance energy transfer immunoassay). In LFRET, fluorophore-labeled protein L and antigen are brought to close proximity by antigen-specific patient immunoglobulins of any isotype, resulting in TR-FRET signal. We set up LFRET assays for antibodies against SP and NP and evaluated their diagnostic performance using a panel of 77 serum/plasma samples from 44 individuals with COVID-19 and 52 negative controls. Moreover, using a previously described SP and a novel NP construct, we set up enzyme linked immunosorbent assays (ELISAs) for antibodies against SARS-CoV-2 SP and NP. We then compared the LFRET assays with these ELISAs and with a SARS-CoV-2 microneutralization test (MNT). We found the LFRET assays to parallel ELISAs in sensitivity (90–95% vs. 90–100%) and specificity (100% vs. 94–100%). In identifying individuals with or without a detectable neutralizing antibody response, LFRET outperformed ELISA in specificity (91–96% vs. 82–87%), while demonstrating an equal sensitivity (98%). In conclusion, this study demonstrates the applicability of LFRET, a 10-min “mix and read” assay, to detection of SARS-CoV-2 antibodies

A 10-Minute “Mix and Read” Antibody Assay for SARS-CoV-2

Accurate and rapid diagnostic tools are needed for management of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Antibody tests enable detection of individuals past the initial phase of infection and help examine vaccine responses. The major targets of human antibody response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the spike glycoprotein (SP) and nucleocapsid protein (NP). We have developed a rapid homogenous approach for antibody detection termed LFRET (protein L-based time-resolved Förster resonance energy transfer immunoassay). In LFRET, fluorophore-labeled protein L and antigen are brought to close proximity by antigen-specific patient immunoglobulins of any isotype, resulting in TR-FRET signal. We set up LFRET assays for antibodies against SP and NP and evaluated their diagnostic performance using a panel of 77 serum/plasma samples from 44 individuals with COVID-19 and 52 negative controls. Moreover, using a previously described SP and a novel NP construct, we set up enzyme linked immunosorbent assays (ELISAs) for antibodies against SARS-CoV-2 SP and NP. We then compared the LFRET assays with these ELISAs and with a SARS-CoV-2 microneutralization test (MNT). We found the LFRET assays to parallel ELISAs in sensitivity (90–95% vs. 90–100%) and specificity (100% vs. 94–100%). In identifying individuals with or without a detectable neutralizing antibody response, LFRET outperformed ELISA in specificity (91–96% vs. 82–87%), while demonstrating an equal sensitivity (98%). In conclusion, this study demonstrates the applicability of LFRET, a 10-min “mix and read” assay, to detection of SARS-CoV-2 antibodies