Impact of Haemophilus influenzae b (Hib) vaccination on meningitis in Central Brazil

OBJECTIVE: To assess the impact of the Haemophilus influenzae b (Hib) conjugate vaccine in reducing the incidence of meningitis among children under five years old. METHODS: A 'before-after' design was used to compare Hib meningitis incidence rates in the pre-vaccine (July 1995 - June 1999) and post-vaccine (July 1999 - June 2001) periods in the state of Goias, central Brazil. Bacterial meningitis case definition was based on World Health Organization criteria. Incidence rates of S. pneumoniae and N. meningitidis were used for comparison purposes. Chi-squared and Student's t tests were used for statistical analysis. P-values below 0.05 were considered as statistically significant. RESULTS: 979 children with acute bacterial meningitis were detected throughout the entire period. The incidence rate of Hib meningitis decreased from 10.8 (x10(5)) in the pre-vaccine period to 2.3 (x10(5)) in the 2nd year post vaccination, leading to a risk reduction of 78%, targeted to the 7-23 months age group (p<0.05). A total of 65 cases of Hib meningitis were prevented. An increase in S. pneumoniae meningitis was observed. Vaccine failure was detected in one child. CONCLUSIONS: This study showed that mass immunization with Hib conjugate vaccine brought about an expressive decline in childhood Hib meningitis in Goias soon after the first year. Notwithstanding, an enhancement of surveillance using high-accuracy tools is essential to: (i) detect a possible reemergence of Hib; (ii) identify vaccine failure, and (iii) monitor changes in the H. influenzae serotype profile over time.     

Evaluation of the antiherpetic activity of standardized extracts of Achyrocline satureioides

Traditionally, Achyrocline satureioides or 'marcela' has been used in South America for the treatment of several disorders. For the present study, three spray-dried extracts (N1, N2 and N3) were used, all of them prepared with 50% of an hydroethanolic extract rich in flavonoid compounds and 50% of blends of different adjuvants. The cytotoxic concentration which causes destruction in 50% monolayer cells (CC50) was 62.5 microg/ml for the three extracts. The antiviral activity was evaluated by using two different strains of herpes simplex virus (HSV-1) and the best results were obtained with KOS strain and N2 extract. Studies concerning the mechanism of the antiherpetic activity demonstrated that N2 extracts showed no virucidal effect or activity on cellular receptors. HSV-1 DNA synthesis was not inhibited. The antiherpetic activity occurred between the second and ninth hour of the virus replication cycle, probably indicating a perturbation on late stages of this cycle.     

First-year results of the third stroke registry in Tartu, Estonia

BACKGROUND: The main goal of the Third Stroke Registry in Tartu was to determine the incidence and 28-day case-fatality rates for first-ever stroke in an Estonian population. METHODS: The data collection started on 01.12.2001. All patients with first-ever stroke living in Tartu were registered. RESULTS: During the first year, 234 first-ever stroke cases were registered. The incidence rate of first-ever stroke age-standardised to the European population was 195/100,000, 214 (95% CI, 185-243) for men and 181 (95% CI, 155-208) per 100,000 for women. Sixty-eight patients (29%) died within 28 days of stroke onset. CONCLUSIONS: The incidence and 28-day case-fatality rate of stroke in Estonia are high compared to other countries. It might be related to higher risk factor prevalence, stress and socioeconomic status.     

Moxonidine and rilmenidine injected into the medial septal area reduces the salivation induced by pilocarpine

We determined the effects of moxonidine and rilmenidine 20 nmol (alpha(2)-adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250-300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg(-1) b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (12+/-3 mg min(-1)) vs. control (99+/-9 mg min(-1)). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20+/-5 mg min(-1)) vs. control (94+/-7 mg min(-1)). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60+/-8 and 95+/-10 mg min(-1), respectively). Yohimbine 40 nmol (alpha(2)-adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70+/-6 and 24+/-6 mg min(-1), respectively). Injection of these alpha(2)-adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of alpha(2)-adrenergic and imidazoline agonists' agents inhibit pilocarpine-induced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that alpha(2)-adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially. These receptors of the medial septal area have an inhibitory mechanism on salivary secretion.     

Lifestyle and late effects after poliomyelitis. A risk factor study of two populations

BACKGROUND: Patients with polio often experience new symptoms (muscle weakness, pain, fatigue and respiratory problems) many years after the acute disease. This study examined possible interactions between lifestyle factors (overweight, physical inactivity, smoking) and late polio with new symptoms. METHODS: A total of 148 patients hospitalized for acute polio in 1950-1954 at Haukeland University Hospital, Norway and 128 patients, hospitalized for acute polio in 1958 at Tartu University Hospital, Estonia responded to a mailed questionnaire regarding lifestyle and late polio with new symptoms. Multiple regression analysis, two samples t-test and chi-square analysis were undertaken. RESULTS: Mean body mass index (BMI) and percentage of smokers did not differ in the two cohorts, while polio patients were physically less active in Estonia. The physically active patients in both cohorts had significantly lower odds for experiencing polio-related late muscle pain (OR = 0.21; 95% CI = 0.08-0.55) and fatigue (OR = 0.32; 95% CI = 0.14-0.75). With increasing age the patients had significantly higher odds for experiencing new muscle weakness (OR = 1.03; 95% CI = 1.00-1.07), fatigue (OR = 1.04;95% CI = 1.01-1.07) and breath shortness (OR = 1.04; 95% CI = 1.00-1.07). CONCLUSION: Physically inactive patients are at a higher risk for late polio-related symptoms. An active lifestyle should be recommended for patients with polio sequels.     

Improving lipoplex-mediated gene transfer into C6 glioma cells and primary neurons

The development of methodologies for gene transfer into the central nervous system is crucial for gene therapy of neurological disorders. In this study, different cationic liposome formulations were used to transfer DNA into C6 glioma cells and primary hippocampal and cortical neurons by varying the nature of the helper lipid (DOPE, Chol) or a mixture of DOPE and cholesterol (Chol) associated to DOTAP. In addition, the effect of the lipid/DNA (+/-) charge ratio, the association of the ligand transferrin to the lipoplexes, and the stage of differentiation of the primary cells on the levels of transfection activity, transfection efficiency, and duration of gene expression were evaluated. Mechanistic studies were also performed to investigate the route of delivery of the complexes into neurons. Our results indicate that DOTAP:Chol (1:1 mol ratio) was the best formulation to transfer a reporter gene into C6 glioma cells, primary hippocampal neurons, and primary cortical neurons. The use of transferrin-associated lipoplexes resulted in a significant enhancement of transfection activity, as compared to plain lipoplexes, which can be partially attributed to the promotion of their internalization mediated by transferrin. While for hippocampal neurons the levels of luciferase gene expression are very low, for primary cortical neurons the levels of transgene expression are high and relatively stable, although only 4% of the cells has been transfected. The stage of cell differentiation revealed to be critical to the levels of gene expression. Consistent with previous findings on the mechanisms of cell internalization, the experiments with inhibitors of the endocytotic pathway clearly indicate that transferrin-associated lipoplexes are internalized into primary neurons by endocytosis. Promising results were obtained in terms of the levels and duration of gene expression, particularly in cortical neurons when transfected with the Tf-associated lipoplexes, this finding suggesting the usefulness of these lipid-based carriers to deliver genes within the CNS.     

E-cadherin loss rather than beta-catenin alterations is a common feature of poorly differentiated thyroid carcinomas

AIMS: To investigate the immunohistochemical and molecular genetic features of the cadherins/catenins complex in thyroid carcinoma based on the hypothesis that poorly differentiated carcinoma of the thyroid represents an intermediate step between well-differentiated and undifferentiated carcinomas. METHODS AND RESULTS: Immunohistochemistry for E-, P- and N-cadherins and alpha-, beta- and gamma-catenins was performed in a series of 17 cases of poorly differentiated carcinoma of the thyroid. All cases showed absence of membranous expression of E-cadherin with no aberrant expression of P- or N-cadherins; regarding catenins there was heterogeneous loss of expression with membranous immunolocalization of the three catenins in most cases. Molecular analysis of the E-cadherin gene and exon 3 of the beta-catenin gene was also performed by polymerase chain reaction/single-strand conformation polymorphism and sequencing. No mutations in either gene were detected in any case. CONCLUSIONS: In contrast to previous reports, our results suggest that loss of E-cadherin rather than beta-catenin mutation is the crucial event in determining the differentiation 'level' of thyroid carcinomas.     

Metoclopramide-induced hyperprolactinemia affects mouse endometrial morphology

Information about the effects of pituitary hyperprolactinemia on endometrium, especially in levels coexisting with absence of amenorrhea in women, is scarce. The interference of high prolactin levels on endometrial morphology was thus investigated in young post-pubertal and adult mice rendered hyperprolactinemic by long-term treatment with metoclopramide (MC). No remarkable differences have been noticed upon light microscopy examination of the endometria comparing young to adult cycling MC-treated mice, except on the max/min diameter ratio, which in young animals was lower than in adults (ANOVA, p < 0.01). Both young and adult MC-treated mice presented an increased number of endometrial glands than their respective controls (ANOVA, p < 0.01). However, young MC-treated animals showed the highest values of endometrial thickness index compared to other groups (ANOVA, p < 0.01). Our results indicate that MC-induced hyperprolactinemia causes mouse endometrium proliferation, mainly in young animals.     

Landing of immune receptors and signal proteins on lipid rafts: a safe way to be spatio-temporally coordinated?

In the past decade one of the cell biology's breakthroughs was discovery of membrane microdomains (rafts, caveolae) and recognition of their important in cellular signaling and protein traffic. In the present minireview a short comprehensive overview is given about physico-chemical, structural and functional properties of rafts. In addition to the classical immunochemical techniques the latest physcial and biophysical technologies that can be used to study these microdomains are also described briefly. The funcational significance of rafts in signaling of multichain immune recognition receptors (MIRRs), the IL-2R and ErbB family factor receptors is also discussed herein together with the still open questions and future prospects of the raft hypothesis.     

Pharmacokinetic-pharmacodynamic interrelationships of intravenous and oral levosimendan in patients with severe congestive heart failure

OBJECTIVE: To assess the pharmacokinetic-pharmacodynamic (PK-PD) interrelations after a 6-hour continuous infusion and a 2 mg single oral dose of levosimendan in patients with congestive heart failure (CHF). METHODS: This was an open-label, non-randomized Phase II trial in 29 patients with New York Heart Association (NYHA) class III-IV CHF, comprising 2 study days. On the first day, patients were given 6-hour levosimendan infusion with the dose 0.2 microg/kg/min. After a 1-week washout, the patients received a 2 mg single oral dose of levosimendan. Heart rate-corrected electromechanical systole QS2i was the primary variable. Secondary variables were heart rate (HR), systolic (sBP) and diastolic blood pressure (dBP) and 24-hour ambulatory ECG (Holter). RESULTS: QS2i shortened from 515 ms at baseline to 506 ms at the end of 6-hour infusion (p = 0.007). After 2 mg single dose, QS2i shortened at 2 h after drug intake from 532 ms at baseline to 525 ms (p = 0.006). The effect was similar also at 8 h (532 ms vs 526 ms, p = 0.017). Mean of maximum shortening of QS2i observed during the infusion was 22 ms (p < 0.0001) and 17 ms after 2 mg single oral dose (p < 0.0001). The concentration-effect loops for QS2i showed a clear counter-clockwise hysteresis with both modes of administration. sBP and dBP decreased both during infusion and after 2 mg oral dose. HR remained unchanged during both modes of administration. CONCLUSIONS: Both 6-hour infusion and 2 mg single dose of levosimendan showed that levosimendan possesses moderate inotropic and vasodilatory effects in patients with severe congestive heart failure, which could be described as counter-clockwise hysteresis. It seemed that the vasodilatory effect appeared earlier than the inotropic effect.