Changes in lipid fractions of blood during the treatment of hypertension with prazosin and trasicor

The paper deals with the study into the benefits of prazosin and trasicor used in arterial hypertension. Their effects on the blood lipid composition were evaluated. With prazosin, the steady antihypertensive effect was reached in 81.0%, whereas with trasicor, it was attained in 46%. When prazosin was given, total cholesterol and triglycerides were statistically significantly decreased by 6.8 and 14.8%, respectively, while high density lipoproteins was increased by 9.1%. When trasicor was administered, no changes were observed in the spectrum of serum lipids. Thus, prazosin is effective in correcting two major risk factors for coronary heart disease, namely arterial hypertension and hyperlipoproteinemia, thereby reducing a risk for coronary heart disease.     

On the effect of chemically activated fine muscle afferents on interneurones mediating group I non-reciprocal inhibition of extensor ankle and knee muscles in humans

In a previous paper it was shown that muscle nociceptive discharge depressed the activity of interneurones mediating group I non-reciprocal inhibition (or Ib interneurones) in humans [A. Rossi, B. Decchi, Changes in Ib heteronymous inhibition to soleus motoneurons during cutaneous and muscle nociceptive stimulation in humans, Brain Res. 774 (1997) 55–61.]. However, since nociceptive discharge depressed the size of the soleus H-reflex (by which Ib inhibition was tested) the question arises as to whether modification of motoneurone membrane conductance per se could depress the size of Ib inhibitory post-synaptic potentials. The results of the present study suggest that the contribution of motoneurone hyperpolarization to Ib disinhibition is negligible and that muscle nociceptive discharge actually depresses the activity of these pathways.     

α-terpineol reduces mechanical hypernociception and inflammatory response

α‐Terpineol (TPN), a volatile monoterpene alcohol, is relatively non‐toxic and one of the major components of the essential oils of various plant species. In this study, we tested for the antihypernociceptive activity of TPN (25, 50 or 100 mg/kg, i.p.) in mice using mechanical models of hypernociception induced by carrageenan (CG, 300 μg/paw) and the involvement of important mediators of its cascade signalling, such as tumour necrosis factor‐α (TNF‐α, 100 pg/paw), prostaglandin E₂ (PGE₂, 100 ng/paw) or dopamine (DA, 30 μg/paw). We also investigated the anti‐inflammatory effect of TPN on the model of carrageenan‐induced pleurisy and the LPS‐induced nitrite production in murine macrophages. Pre‐systemic treatment with TPN (25, 50 or 100 mg/kg, i.p.) inhibited the development of mechanical hypernociception induced by CG or TNF‐α. A similar effect was also observed upon PGE₂ and DA administration. In addition, TPN significantly inhibited the neutrophil influx in the pleurisy model. TPN (1, 10 and 100 μg/mL) also significantly reduced (p < 0.01) nitrite production in vitro. Our results provide information about the antinociceptive and anti‐inflammatory properties of TPN on mechanical hypernociception and suggest that this compound might be potentially interesting in the development of new clinically relevant drugs for the management of painful and/or inflammatory disease.     

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua,Mexico

Background

Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures.

Objective

This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk.

Methods

We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine.

Results

After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine.

Conclusions

Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol.

Citation

Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.1408742     

Detection and evaluation of endocrine-disruption activity in water samples from Portuguese rivers

Water samples (n = 183) from Portuguese rivers were tested for the presence of endocrine disruptors using the recombinant yeast assay (RYA) combined with chemical identification of compounds having endocrine-disruption properties by liquid chromatography coupled to mass spectrometry. Ten selected locations were sampled monthly for a period of 20 months, from April 2001 to December 2002. More than 90% of samples showed either no detectable or low levels of estrogenicity (<0.1 ng/L of estradiol equivalents). The remaining samples (17 in total, 9.3%) showed estrogenicity values ranging from 0.1 to 1.7 ng/L of estradiol equivalents; only two samples showed values greater than 1 ng/L of estradiol equivalents. Most highly estrogenic samples (13 of 17 samples) originated in five sampling sites clustered in two zones near Porto and Lisbon. Chemical analysis detected alkylphenolic compounds (octyl- and nonylphenol plus nonylphenol ethoxylates) in all samples, albeit at concentrations less than 1 microg/L for each compound in 80% of samples. Total analyte concentration exceeded 10 microg/L in only 10 samples, with all but one of those originating from only two sampling sites. In these two locations, a good correlation was observed between the concentrations of octylphenol, nonylphenol, and to a lesser extent, bisphenol A in the samples and their estrogenicity values as calculated by RYA. We conclude that estrogenic activity can be explained by alkylphenol contamination in only these sites; for the remainder, we propose that pesticides and urban waste may be the main factors responsible for estrogenic contamination.     

Prevalence of Trachoma in Jigawa State,Northwestern Nigeria

ABSTRACT

Purpose: To determine the magnitude of trachoma and the prevalent forms of the disease, and to provide baseline data for the establishment of a trachoma control program in Jigawa State, northwestern Nigeria.

Methods: A population-based cross-sectional survey was conducted in Jigawa State in May 2007 using a 2-stage cluster random sampling technique to select 4598 persons from 40 villages based on probability proportional to size. All participants were examined using a penlight and a 2.5?×?binocular loupe for signs of trachoma, and graded using the World Health Organization (WHO) simplified grading system.

Results: A total of 4598 people were seen with 99.96% coverage. Of these, 2460 (53.5%) were female and 2138 (46.5%) were male. Mean age was 21.6 years (?±?19.8 years). The prevalence of follicular trachoma in children aged ≤9 years was 20.5% (95% confidence interval, CI, 18.7–22.4%) with no difference between the sexes. The prevalence of trichiasis in adults aged ≥15 years was 5%, and the prevalence was higher in females than males (odds ratio 2.60, 95% CI 2.06–3.28; p?<?0.001).

Conclusion: Trachoma is a major problem in Jigawa State; there is a need to train trichiasis surgeons and empower them to carry out community-based surgery. District-level prevalence of trachoma needs to be determined to know which aspects of the WHO SAFE strategy (surgery, antibiotics, facial cleanliness and environmental improvements) need to be emphasized in each district.     

Unravelling the cardiovascular effects induced by α‐terpineol: A role for the nitric oxide–cGMP pathway

1. α‐Terpineol is a monoterpene found in the essential oils of several aromatic plant species. In the present study, we investigated the mechanisms underlying the cardiovascular changes induced by α‐terpineol in rats. 2. In normotensive rats, administration of α‐terpineol (1, 5, 10, 20 and 30 mg/kg, i.v.) produced a dose‐dependent hypotension (?10 ± 3, ?20 ± 8, ?39 ± 16, ?52 ± 21 and ?57 ± 23 mmHg, respectively; n = 5) followed by tachycardia. The hypotensive responses to 1, 5, 10, 20 and 30 mg/kg, i.v., α‐terpineol were significantly attenuated following the administration of N^G‐nitro‐l‐ arginine methyl ester (l ‐NAME; 20 mg/kg, i.v.; ?2 ± 1, ?5 ± 2, ?7 ± 3, ?22 ± 9 and ?22 ± 10 mmHg, respectively; P < 0.05; n = 5). 3. In 10 μmol/L phenylephrine (PE)‐precontracted mesenteric artery rings, α‐terpineol (10^?12 to 10^?5 mol/L) caused a concentration‐dependent relaxation (maximum relaxation 61 ± 6%; n = 7). After removal of the endothelium, the vasorelaxation elicited by α‐terpineol was attenuated (maximum relaxation 20 ± 1%; P < 0.05; n = 7). In addition, vasorelaxation induced by α‐terpineol in rings pretreated with 100 or 300 μmol/L l ‐NAME, 30 μmol/L hydroxocobalamin or 10 μmol/L 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one was attenuated (maximum relaxation 18 ± 3, 23 ± 3, 24 ± 7 and 21 ± 1%, respectively; n = 6; P < 0.05). 4. Furthermore, in a rabbit aortic endothelial cell line, 10^?6, 10^?5 and 10^?4 mol/L α‐terpineol induced concentration‐dependent increases in nitric oxide (NO) levels (12 ± 6, 18 ± 9 and 34 ± 12%Δ fluorescence, respectively; n = 3). 5. In conclusion, using combined functional and biochemical approaches in the present study, we were able to demonstrate that α‐terpineol‐induced hypotension and vasorelaxation are mediated, at least in part, by the endothelium, most likely via NO release and activation of the NO–cGMP pathway.     

Hypotensive and Vasorelaxant Effects of Citronellol,a Monoterpene Alcohol,in Rats

Abstract: Citronellol is an essential oil constituent from the medicinal plants Cymbopogon citratus, Cymbopogon winterianus and Lippia alba which are thought to possess antihypertensive properties. Citronellol‐induced cardiovascular effects were evaluated in this study. In rats, citronellol (1–20 mg/kg, i.v.) induced hypotension, which was not affected by pre‐treatment with atropine, hexamethonium, N^ω‐nitro‐l ‐arginine methyl ester hydrochloride or indomethacin, and tachycardia, which was only attenuated by pre‐treatment with atropine and hexamethonium. These responses were less than those obtained for nifedipine, a reference drug. In intact rings of rat mesenteric artery pre‐contracted with 10 μM phenylephrine, citronellol induced relaxations (pD₂ = 0.71 ± 0.11; E_max = 102 ± 5%; n = 6) that were not affected by endothelium removal, after tetraethylamonium in rings without endothelium pre‐contracted with KCl 80 mM. Citronellol strongly antagonized (maximal inhibition = 97 ± 4%; n = 6) the contractions induced by CaCl₂ (10^?6 to 3 × 10^?3 M) and did not induce additional effects on the maximal response of nifedipine (10 μM). Finally, citronellol inhibited the contractions induced by 10 μM phenylephrine or 20 mM caffeine. The present results suggest that citronellol lowers blood pressure by a direct effect on the vascular smooth muscle leading to vasodilation.     

Antinociceptive and anticonvulsant effects of the monoterpene linalool oxide

Context: Linalool oxide (OXL) (a monoterpene) is found in the essential oils of certain aromatic plants, or it is derived from linalool. The motivation for this work is the lack of psychopharmacological studies on this substance.

Objective: To evaluate OXL’s acute toxicity, along with its anticonvulsant and antinociceptive activities in male Swiss mice.

Material and methods: OXL (50, 100 and 150?mg/kg, i.p.) was investigated for acute toxicity and in the Rota-rod test. Antinociceptive activity was evaluated by the acetic acid-induced writhing test, and by formalin testing. Anticonvulsant effects were demonstrated by testing for pentylenetetrazol (PTZ)-induced seizures and by Maximum Electroshock headset (MES) test. OXL was administered to the animals intraperitoneally 30?min before for pharmacological tests.

Results: OXL showed an LD₅₀ of ～721 (681–765) mg/kg. In the Rota-rod test, it was observed that OXL caused no damage to the animal’s motor coordination. OXL significantly reduced (p?p?p?p?p?p?p?Conclusion: The tested doses of OXL were safe, with no motor impairment, and show clear antinociceptive and anticonvulsant potential. Future investigations with this monoterpene may lead to the development of a new molecule with even higher potency and selectivity.