Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype

OBJECTIVE: Abnormalities in the natriuretic peptide system could play a key role in the genesis of hypertension. We evaluated the associations between a family history of hypertension, cardiovascular phenotype and allelic variants of Npr1 and Npr3, two candidate genes that codify for natriuretic peptide receptors. METHODS: We genotyped 45 young normotensive subjects (19 males, 26.8 +/- 3.7 years) with accurately assessed family history of hypertension (FH+) and 52 (26 males, 26.1 +/- 3.1 years) without (FH-) for the known variants of Npr1 and Npr3 genes, and for a novel length difference (3C/4C) polymorphism at position 15129 in the 3'-untranslated region of the Npr1 gene. Blood pressure, echocardiography and plasma brain natriuretic peptide were assessed. RESULTS: Both the novel Npr1 3C allele (59 versus 33%, P < 0.001) and the 3C/3C genotype (31 versus 8%; P < 0.001) were significantly more frequent in FH+ than in FH-. The inverse distribution of the 4C/4C genotype suggested that a casual association was very unlikely. Moreover, the 3C/3C homozygous had significantly higher systolic blood pressure (121.1 +/- 6.3 versus 115.6 +/- 7.8 mmHg in 4C/4C; P < 0.05) and a longer left ventricular isovolumic relaxation time (67 +/- 10 versus 61 +/- 9 ms; P < 0.05). The Npr3 C(-55) allele variant was also more frequent in FH+ (88 versus 76%, P < 0.05), but was not associated with the cardiovascular phenotype. CONCLUSIONS: The novel Npr1 gene 3C variant and the Npr3 gene C(-55) allele are associated with hypertensive family history. Moreover, the functional Npr1 3C variant, when homozygous, is also associated with higher systolic blood pressure and prolonged ventricular relaxation.     

EEG power spectra changes and forebrain ischemia in rats

BACKGROUND: Several animal models of cerebral ischemia have been developed to investigate both pathophysiology and pharmacological treatment. The aim of this study was to verify the prognostic value of EEG power spectra analysis in a two-vessel plus hypotension rat model of transient global ischemia. METHODS: Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs) were subjected to 20 min bilateral common carotid artery occlusion plus hypotension by sodium nitroprusside followed by reperfusion for seven days. Sham-operated animals served as controls. The changes after ischemia in EEG power spectra, and their relations with neuronal damage and astrocytic response were investigated. RESULTS: The EEG analysis revealed that in SHRs and WKYs, ischemia produced a dramatic increase in delta activity and a decrease in theta, beta and alpha activities derived from both cortical and hippocampal areas. EEG activity reverted to normal values more quickly in WKYs than in SHRs which did not recover cortical and hippocampal alpha and beta activities even at six days of reperfusion. SHRs presented more severe damage and intense astrocytosis than WKYs in almost all the brain regions analyzed. In SHRs, hippocampal delta activity was positively correlated with the degree of neuronal necrosis and astrocytic activation, whereas theta, alpha and beta activities correlated negatively. No correlations were found in WKYs. CONCLUSIONS: These data indicate that the hippocampal bioelectrical activity recorded in SHRs from the beginning of reperfusion could be useful for predicting the ischemic outcome and evaluating the effects of pharmacological interventions.     

Maternal pulse oximetry perfusion index as a predictor of early adverse respiratory neonatal outcome after elective cesarean delivery.

OBJECTIVE: Evidence suggests increased morbidity, in particular early neonatal respiratory complications, in newborns from elective cesarean section compared with those from vaginal delivery. No reliable maternal predictors of adverse neonatal outcome at elective cesarean section are known. Here, we prospectively tested the hypothesis that a low maternal perfusion index at the baseline phase (i.e., preanesthesia) of the elective cesarean section is a predictor of early adverse neonatal respiratory outcome. DESIGN: Prospective cohort study. SETTING: Operating and delivery rooms of a public health hospital with a tertiary-level neonatal intensive care unit. PATIENTS: Forty-four healthy pregnant women with no known risk factors undergoing elective cesarean section at term gestation. INTERVENTIONS: Elective cesarean section was divided into nine phases. Analysis of pulse oximetry-derived signals (perfusion index, pulse rate, and oximetry) and systolic, diastolic, and differential blood pressure were recorded. Maternal arterial and venous newborn cord blood gas analyses and placental histology were evaluated. MEASUREMENTS AND MAIN RESULTS: Early respiratory complications (transient tachypnea of the newborn, n = 5; respiratory distress syndrome, n = 1) were observed in 13.6% (6 of 44) of the newborns. A maternal perfusion index < or = 1.9 (lower quartile) during the preanesthesia phase of the elective cesarean section was an independent predictor of early adverse neonatal respiratory outcome (odds ratio 68.0, 95% confidence interval 6.02-767.72; p < .0001). CONCLUSIONS: A decreased perfusion index value in the preanesthesia phase of elective cesarean section is a maternal predictor of increased neonatal morbidity and is significantly related to subclinical placental inflammatory disease. These observations suggest the feasibility of a noninvasive pulse oximeter prenatal screening of the high-risk fetus/newborn in elective cesarean section.     

Large-scale screening of the in vitro susceptibility of Prototheca zopfii towards polyene antibiotics

A large scale screening of the in vitro susceptibility of 105 strains of Prototheca zopfii to a panel of polyene antibiotics (amphotericin B, nystatin, primaricin and filipin) was conducted. Strains studied were isolated from dairy-associated environments in five different localities. Groups 1-4 included strains recovered from four separate regions of Italy, while group 5 included isolates from Belgium. Amphotericin B and primaricin exhibited the highest activity, with th MIC90 ranging from 4 and 8 microg/ml, respectively. On the other hand, the MIC90 of nystatin and filipin were from two to four times higher. Two strains were resistant to all four polyenes tested. The above results are compared with those in the literature and the importance of carrying out large-scale screening surveys to assess polyene susceptibility patterns within the species P. zopfii is discussed.     

Controlled trial of long term oral potassium supplements in patients with mild hypertension

A 15 week randomised double blind placebo controlled trial of oral potassium supplements (48 mmol daily) was conducted in 37 patients who had mildly increased blood pressure and a normal dietary intake of sodium. After a two month run in and a one week baseline period the patients were randomly assigned to receive either potassium supplements (n = 18) or placebo (n = 19). By the third week of treatment blood pressure in the actively treated group had decreased significantly compared with that in the placebo group, though the decrease reached its maximum after 15 weeks. Urinary potassium excretion increased significantly in the group who received potassium supplements, but no significant changes were found in plasma sodium and potassium concentrations or in urinary sodium excretion. In a subgroup of 13 patients who underwent a further nine weeks of treatment with oral potassium supplements at half of the previous dose (24 mmol daily) their blood pressure, at the end of this second study period, was still significantly lower compared with their baseline value but not with that of the placebo group. These results show that moderate oral potassium supplements are associated with a long term reduction in blood pressure in patients who have mild hypertension.     

When should “chronic migraine” patients be considered “refractory” to pharmacological prophylaxis?

Patients with chronic headache forms evolving from a previous episodic migraine (‘chronic migraine’) are often difficult to treat. In this paper we focus attention on aspects we believe important for producing a definition of “refractory” in relation to this headache form. We propose a “chronic migraine” patient should be considered “refractory” to pharmacological prophylaxis when adequate trials of preventive therapies at adequate doses have failed to reduce headache frequency and improve headache-related disability and, in patients with medication overuse, reduce the consumption of symptomatic drugs. However before a definition of “refractory” chronic migraine can become established, generally accepted diagnostic criteria and treatment guidelines for this condition need to be developed.

     

The serotonergic system in migraine

Serotonin (5–HT) and serotonin receptors play an important role in migraine pathophysiology. Changes in platelet 5–HT content are not casually related, but they may reflect similar changes at a neuronal level. Seven different classes of serotoninergic receptors are known, nevertheless only 5–HT2B–2C and 5HT1B–1D are related to migraine syndrome. Pharmacological evidences suggest that migraine is due to an hypersensitivity of 5–HT2B–2C receptors. m–Chlorophenylpiperazine (mCPP), a 5–HT2B–2C agonist, may induce migraine attacks. Moreover different pharmacological preventive therapies (pizotifen, cyproheptadine and methysergide) are antagonist of the same receptor class. On the other side the activation of 5–HT1B–1D receptors (triptans and ergotamines) induce a vasocostriction, a block of neurogenic inflammation and pain transmission.     

Accidental hypothermia in a child

We report a case of severe accidental hypothermia (24.8 degrees C) in a seven-year-old child due to prolonged exposure to low temperatures and temporary contact with river water. When the patient was seen in hospital, bradycardia (30.min-1), bradypnoea (5. min-1), scarcely reacting pupils, and Glasgow Coma Scale=3 were noted. For rewarming minimally invasive techniques (humidified warmed gases and intravenous solutions at 40 degrees C) were employed with a very successful outcome.