Impacts of Exogenously Derived Nitrogen Oxide and Sulfur Compounds on the Structure and Function of the Vascular Endothelium Link Pregnancy Hypertension with Later Life Hypertension

The relationship between pregnancy hypertension and later life hypertension is explained by long-term impacts of environmental oxidants on the vascular endothelium. These impacts may precede the onset of the disease as a primary defect and may participate in the pathogenesis of hypertension itself. Continuous exposure to strong exogenous oxidants such as NOx (NO and NO2) reversibly oxidizes oxyhemoglobin (Fe2+) to methemoglobin (Fe3+), and irreversible methemoglobinemia can arise because of disruption of the oxidant/antioxidant balance supported by SO2 metabolites, as inhibitors of antioxidants, and by synergistic degradation of antioxidant thiols. Methemoglobin by itself and from heme, redox-active ferric iron as product of methemoglobin catabolism, have prooxidant properties and cause important structural and functional changes in the vascular endothelium such as growth arrest, senescence, morphological alterations and cell apoptosis. In 1975, an epidemiological study among 204 pregnant women in Labin (Croatia) identified 30 (14.7%) cases of preeclampsia and 25 (12.3%) cases of hypertension in pregnancy. Ten years later, we found a significant number of hypertension cases (N=5; P=0.0027), and among them, we found a significant number of pregnancy-induced hypertension cases (N=3; P=0.0003) and a significant number of psychoneurotic disturbances (P=0.0190), but these conditions were not found in the normotensive women ten years after giving birth (P = 0.1161). Our original findings confirm that hypertension in pregnancy is not a transient impairment but instead is an extension of the effects of exogenously induced oxidative stress on the structure and function of the vascular endothelial, and indicate delayed effects plausibly manifesting as hypertension in later life

Intracranial tumors in adult population of the Varaždin County (Croatia) 1996-2004: a population-based retrospective incidence study

Aim: To estimate the incidence of intracranial tumors in the adult population of the Varazdin County, Croatia, for the 1996-2004 period. - - - - - Methods: Setting: Varazdin County General Hospital and four university hospitals in Zagreb, the capital of Croatia. Study period: January 1, 1996 to December 31, 2004. Incident patients: county residents admitted for newly diagnosed intracranial tumors according to the WHO diagnostic criteria. Demographic data were extracted from the 2001 Croatian census. Incidence rates (IRs) per 100,000 person-years (p-y) and annual IRs (per 100,000 persons) were determined and compared as incidence rate ratios (IRRs) with 95% CI. - - - - - Results: For primary intracranial tumors (PITs), IR was 12.1/100,000 p-y (95% CI: 10.3-14.2), comparable in men and women. The highest incidence was recorded for glioblastoma (IR 4.8, 3.7-6.2) and meningioma (IR 3.1, 2.2-4.2). The incidence of PIT was somewhat greater than that of metastatic tumors (IRR 1.58, 95% CI: 1.22-2.05, P = 40 vs. population aged <= 39 (all IRRs with 95% CI greater than 1, P < 0.05 or < 0.001), comparable in men and women. Women were somewhat older than men at the time of diagnosis of PIT: median difference -6 years (95.1% CI: -10 to -1, P < 0.05). Annual IRs for all these tumor categories showed increasing trends over the study period. - - - - - Conclusion: Overall, there was an increasing trend in the incidence of primary intracranial tumors in the Varazdin County. Data did not allow estimation for most of the specific tumor types

Methemoglobinemia &#8212; A biomarker and a link to ferric iron accumulation in Alzheimer&#8217;s disease

Understanding the mechanism of oxidative stress is likely to yield new insights regarding the pathogenesis of Alzheimer\u2019s disease (AD). Our earlier work focused on the difference between hemoglobin and methemoglobin degradation, respectively leading to ferrous (Fe2+) iron, or ferric (Fe3+) iron. Methemoglobin has the role of carrier, the donor of cytotoxic and redox-active ferric (Fe3+) iron, which can directly accumulate and increase the rate of capillary endothelial cell apoptosis, and may cross into the brain parenchyma, to the astrocytes, glia, neurons, and other neuronal cells (neurovascular unit). This supposition helps us to understand the transport and neuronal accumulation process of ferric iron, and determine how iron is transported and accumulated intracellularly, identifiable as \u201cBrain rust\u201d. Earlier research found that the incidences of neonatal jaundice (p = 0.034), heart murmur (p = 0.011) and disorders such as dyslalia and learning/memory impairments (p = 0.002) were significantly higher in those children born from mothers with methemoglobinemia. Our hypothesis suggests that prenatal iron abnormalities could lead to greater neuronal death, the disease ageing process, and neurodegenerative disorders such as AD and other neurodegenerative diseases