Innate immune receptor expression in normal brain aging.

Brain aging often results in cognitive impairment and is considered to be a major risk factor for neurodegenerative diseases. Earlier studies reported inflammatory responses in aged brain that could contribute to age-related neurodegeneration. Recently, innate immune receptors such as toll-like receptors (TLRs), so far implicated in defense against microorganisms, have been linked to pathogenesis of Alzheimer's disease. Therefore, we asked whether the transcription of TLRs (1-9) and CD14, could also be altered in physiological brain aging. Using real-time polymerase chain reaction (PCR), we indeed observed that TLR1, TLR2, TLR4, TLR5, TLR7 and CD14 expression was up-regulated in mouse brain in correlation with age. In contrast, transcriptions of TLR3, TLR6 and TLR8 were unchanged and the one of TLR9 was down-regulated. In situ hybridization further confirmed these results and identified the cellular source of TLR2 and TLR7 as mononuclear phagocytes. Together, this first systematic analysis demonstrates altered regulation of those innate immune receptors even in normal brain aging, which might be of relevance for understanding susceptibility to neurodegenerative processes associated with aging.

Hepatitis A control in a refugee camp by active immunization.

An outbreak of hepatitis A occurred among children of a refugee camp in Croatia. In order to disrupt the outbreak, we decided to vaccinate children from 1 to 15 years of age in the camp, in addition to intensified general preventive measures. Assuming high prevalence of hepatitis A virus antibodies within this population, we conducted anti-HAV testing of the children eligible for vaccination. Of 108 children tested, 74 (68.5%) were anti-HAV positive. We vaccinated 34 children. One month after vaccination 31 previously negative children were tested for anti-HAV and 30 of them were found positive, suggesting a seroconversion rate of 96.8%. One child fell ill 5 days after vaccination, after whom no new cases of hepatitis A occurred. Thus we conclude that active immunization is a successful means of stopping an outbreak of hepatitis A.

Decreasing risk of viral transfusion-transmitted diseases in Croatia.

AIM: To assess the risk of viral transfusion-transmitted infections in Croatia. METHODS: The following parameters were analyzed: frequency of blood donations repeatedly reactive for HBsAg and anti-HCV (1993-1999); blood donations confirmed positive for HBsAg and anti-HCV (1997-1999), anti-HIV1/2, and syphilis reactivity (1993-1999); number of registered patients with hepatitis B and C; transfusion-associated hepatitis B and hepatitis C; and frequency of HBV, HCV and HIV markers in patients with congenital bleeding disorders (1993-1998). RESULTS: The frequency of repeatedly reactive HBsAg and anti HCV markers and confirmed positive HBsAg, anti-HCV, and syphilis markers in donors blood decreased during the study, whereas the frequency of anti-HIV1/2 positivity did not change. The frequency of confirmed positive donors in 1999 was 0.068% for HBsAg, 0.035% for anti HCV, 0.002% for anti HIV1/2, and 0.0056% for syphilis. The number of patients with hepatitis B, hepatitis C, and transfusion-associated hepatitis B and C steadily decreased during the 1993-1998 period. The number of transfusion-associated hepatitis patients leveled off in 1997. From the beginning of the follow-up of AIDS patients in 1987, only 7 (2%) of hemophiliacs have been HIV-infected, all before 1990 and due to non-inactivated coagulation factor concentrates. There were no cases of transfusion-associated HIV2 infection in patients with congenital bleeding disorders or transfusion-associated HIV1 infection through transfusion of labile blood components. CONCLUSION: The safety of transfusion therapy in Croatia has improved, and the present risks of viral transfusion transmitted diseases are very low.

Influence of prolonged stress on risk factors for cerebrovascular disease.

The main purpose of this study was to analyze the influence of psychological and socio-economic factors on the frequency and characteristics of risk factors for cerebrovascular disease (CVD) among Croatians. A group of 120 war sufferers with signs of post-traumatic stress disorder and adaptation disturbances have been studied, and compared with a control group of 120 persons with no traumatic war experience. The risk factors for CVD were registered using epidemiological, clinical and functional measures, and level of the risk. In a displaced persons group a significant higher rates (p < 0.05) of arterial hypertension (AH), hyperlipidemia and obesity are found, with particularly higher rates of occurrence of AH and hyperlipidemia in younger individuals. Alcoholism was more frequent in the control group. Total risk for stroke was higher in the exposed group. The authors conclude that there is a need for undertaking intensive preventive measures in the risk population exposed to chronic stress and negative socioeconomic life conditions.

IgG serology pattern in long-term follow-up of patients successfully treated for Helicobacter pylori eradication.

A long-term specific IgG serology pattern after successful eradication of Helicobacter pylori using Pyloriset EIA-G with acid-glycine extracted antigen is shown. A total of 214 HP-seropositive dyspeptic patients, mean age 51, were included. Despite individual variability among patients, calculation of antibody decline in each individual, 2, 4, 6, 12, 18, and 24 months after treatment, the authors observed that overall mean decline in the group as a whole was 49%, 67%, 78% 87%, 91%, and 93%, respectively. Unlike Cutler and coworkers, the authors found a regular constant IgG-decline in successfully treated patients until seroconversion. The time to reach seroconversion was found to depend on the pretreatment level of specific IgG. In the groups of patients with baseline IgG less than 1300, 42/44 (95%) seroconverted within the first year of monitoring. When long-term monitoring is needed, unnecessary multiple biopsies can be avoided by use of quantitative IgG serology.

Influence of prolonged stress on cerebral hemodynamics.

The author has investigated the impact of psychological and socio-economic factors on cerebral hemodynamics and development of cerebrovascular disease (CVD). A group of 120 war sufferers with signs of post-traumatic stress disorder and adaptation disturbances, and 120 persons of the control group with no traumatic war experience have been studied. The blood flow velocity and various parameters of spectral frequency analysis have been measured, using the method of transcranial doppler sonography (TCD). A greater number of hemodynamical changes has been found in the group of subjects than in the control group (p < 0.05), in which increase of vasospasm is statistically significant probably as a result of predomination of the sympathetic system stimulation and nicotinic effect on the brain blood vessels. Flow disturbances are relatively more frequent in older subjects, which suggests the rapid development of the atherosclerotic process. The results suggest that exposure to prolonged stress and bad socio-economic factors, through different neurobiological mechanisms, increased the risk for stroke.

[Reactivity and immunogenicity of Havrix 360 vaccine for hepatitis A]. / Reaktogenost i imunogenost "Havrix 360" vakcine protiv hepatitisa A.

The reactogenicity and immunogenicity of a new vaccine against viral hepatitis A, under the name HAVRIX, manufactured by SmithKline Beecham Biologicals, Belgium, was studied. A single dose of 1 ml contains not less than 360 ELISA units of inactivated HAV, strain HM175, cultivated on human diploid cells. The vaccine has been applied intramuscularly to 80 second-grade primary school children under the 0, 1 and 6-month schedule. Postvaccinal reactions were followed for three days after each application of the vaccine. They were generally mild and present in less than 5% of the vaccinees (local as well as general). One month after the last vaccination the seroconversion was 100% in the anti HAV antibody test (HAVAB-ABBOT), the antibody level being over 500 IU/I, in 98% of the vaccinees. In conclusion, the tested vaccine is perfectly acceptable from both aspects, postvaccinal reactions and conferred protection. As the hepatitis A morbidity in Croatia has never been as low as in the last few years, the eventual introduction of this vaccination into the EPI is questionable.

Prevalence of markers of hepatitis B virus infection among the general population of the municipality of Slavonski Brod.

To assess the prevalence of hepatitis B viral infection in general population of the Community of Slavonski Brod, sera from 2,142 apparently healthy individuals were tested for the hepatitis B virus (HBV) markers: surface antigen and antibody (HBsAg and anti-HBs), and core antibody (anti-HBc), by radio and enzyme-immunoassay. The HBsAg results showed a general prevalence of 1.8%(38/2,142): for males 1.9% and for females 1.6%. The highest HBsAg incidence rates (2.1% and 1.9%) were found in young adults aged 21-30, respective in older children and adolescents, from 11 to 20 years. The lowest HBsAg prevalence (1.0%) was proved in children from 1 to 5 years, while in sera of 68 examined sucklings HBsAg was not detected. The HBsAg incidence was 1.9% (21/1132) in urban and 1.7% (17/1010) in rural inhabitants. The overall prevalence rate of total HBV infection in 13.7% (294/2,142) examinees was found. There was no difference in the prevalence of HBV infection in males 15.7% (177/1130) and females 11.6% (117/1012), as well as in persons living in rural 12.5% (126/1010) or in urban 14.8% (168/1132) areas. The prevalence rate of anti-HBs and anti-HBc gradually increased with increasing age, starting at about 3.2% in the youngest, and reaching 15.5% in adults over 50 years. The results obtained have place the Community of Slavonski Brod among areas with an intermediate endemicity of HBV infection.

[The combined immunoenzyme test: anti-HIV-1 and -2 and anti-HTLV-1 in the detection of donors with retrovirus infections]. / Ispitivanje kombiniranog enzimskog imunoloskog testa: anti-HIV 1/2 i anti HTLV-1 u otkrivanju davatelja zarazenih retrovirusima.

Serums of whole blood donors, plasma donors, hemophiliacs, persons with risks behavior and normal population simultaneously were tested for markers of infectious diseases, anti-HIV-1 with Plivazim and anti-HIV-1/2 and anti-HTLV-1/2 with Roche Retrovirus EIA. The positive results were confirmed by immunofluorescence assay and Western blot. Nonspecific reactive serums were detected by Roche Retrovirus EIA and by Plivazim EIA, but there was no significant difference in the frequence of reactive results. Roche Retrovirus EIA test had specificity of 99.16% and sensibility of 97.56% as compared to Plivazim. Simultaneous testing of donors with a combined test for anti-HIV-1/2 and anti-HTLV-1 is equally reliable as testing with only anti-HIV-1.

The significance of immunocompromised condition in the prophylaxis of hepatitis B in chronic renal insufficiency.

The paper presents the immunogenicity of hepatitis vaccine (obtained by genetic engineering) in immunocompromised patients with preterminal renal insufficiency defined by depression of creatinine clearance of 10 to 25 ml/min. The study consisted of 28 randomized patients with impaired renal function. Sixteen patients received a single dose and, twelve a double dose of vaccine. Revaccination following 3 intramuscular doses of vaccine had been undertaken after 24 weeks if antibodies were not detected or their titer was 10 i. u. or less. All patients obtained a booster dose following 52 weeks. There was no statistically significant difference in titer values between immunocompromised patients regardless of whether they were vaccinated with a single or double dose. The antibody titer in patients with chronic renal insufficiency was significantly lower as compared with the results of vaccination in healthy population. It may be concluded that it is more beneficial and less expensive to use a single dose vaccine and revaccination if the titer is negative or insufficiently high.

[Reactivity and immunogenicity of Engerix B, the recombinant DNA vaccine against hepatitis B]. / Ispitivanje reaktogenosti i imunogenosti rekombinantne DNA vakcine protiv hepatitisa B "Engerix-B".

A group of 67 health workers with no markers indicating previous hepatitis B infection were vaccinated against hepatitis B with a new DNA recombinant vaccine, Engerix B (commercially manufactured by Smith-Kline-RIT, Belgium). Three injections were given according to the 0-1-6 schedule. One month after the last injection the vaccinees were tested for anti-HBs antibodies by the enzyme-linked assay. Antibody titers equal or less than 10 mIU/ml were found only in three subjects or in 4.5% of them. Titers ranging from 11 to 99 mIU/ml were found in 7 subjects (10.4%), from 100 to 999 mIU/ml in 28 (41.8%) and those equal or more than 1000 mIU/ml in 29 subjects (43.3%). It is inferred that the seroconversion rate is 95.5%. Only one subject did not develop detectable antibodies but three subjects had titers over 10000 mIU/ml. No one developed overt hepatitis B during the trial nor did the high responders experienced inapparent infections. They were tested for anti HBc with negative results. Postvaccinal reactions were mild and almost exclusively local. There were no complications. For its high immunogenicity and acceptable reactogenicity the Engerix B vaccine has a promising future.