Enrique Terán

Treatment of cutaneous leishmaniasis with nitric-oxide donor

Nitric oxide (NO) released by activated murine macrophages exerts a powerful cytostatic and cytotoxic effect against a variety of pathogens, including Leishmania major. We have investigated whether S-nitroso-N-acetylpenicillamine (SNAP), a compound that generates NO, could be a therapeutic agent in human cutaneous leishmaniasis. 16 Ecuadorean patients (4–37 years old) were selected by the following inclusion criteria: the presence of only one skin ulcer (14–26 mm largest diameter), positive staining for leishmania amastigotes in lesion exudate, and no drug treatment. To confirm the diagnosis, a tissue sample was obtained from the centre of the ulcer with a 4 mm diameter disposable biopsy punch. The sample was cultured in a Novy-MacNeal-Nicolle medium for 10 days, after which time the presence of leishmania was determined. The appearance of a single 70 bp amplification product following the polymerase chain reaction identified the leishmaniasis as the braziliensis variety in all cases. A cream of SNAP (donated by Glaxo Wellcome) with a final concentration of 200 μmol/L was prepared using cetyl alcohol (1hexadecanol), quarternary ammonium, and distilled water. Release of NO by the cream was verified by testing an aqueous extract for its vasodilator and antiaggregatory actions. The aqueous extract was active for 4 h after dissolving the cream; however, the undiluted cream did not lose activity over 30 days. The SNAP cream was administered topically to the lesion every 4 h (except during sleep) for a total of 10 days. The progression of the ulcer was assessed visually by the same investigator (CR) during treatment. The protocol for the study was approved by the ethics committee of the Instituto de Investigaciones para el Desarrollo de la Salud (IIDES), Ministerio de Salud Publica del Ecuador. After 5 days, improvement of the ulcer and the presence of granulation were evident in all patients and after 10 days the ulcer evolved into granulation tissue. By 30 days all lesions were healed and new skin could be observed. There was no improvement in five patients who received vehicle alone. Side-effects were not observed, apart from a transient warm sensation on the lesion immediately after application of the cream. The clinical improvement was confirmed by the absence of leishmania in cultures of a second biopsy RESEARCH LETTERS

Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia.

To assess whether supplementation with Coenzyme Q10 (CoQ10) during pregnancy reduces the risk of pre‐eclampsia.

Improvement in Functions of the Central Nervous System by Estrogen Replacement Therapy Might Be Related with an Increased Nitric Oxide Production

Estrogen promotes neurons growth, prevents neuronal cell atrophy and regulates synaptic plasticity. Administration of estrogen protects neurons against oxidative stress, excitotoxins, and beta-amyloid-induced toxicity in cell culture. It has been shown that estrogen treatment reduces the serum monoamino oxidase levels and might regulate learning and memory. Nitric oxide (NO) is a retrograde messenger and long-term potentiation can be block using NO-synthase inhibitors or can be prevent with NO-scavengers. NO synthase is widespread in the central nervous system and acts as neurotransmitter/neuromodulator. The actions of serotonin, bradykinin, endothelin, acetylcholine and noradrenaline might be linked to NO formation. Estrogen induces activity of constitutive NO synthase and estrogen replacement therapy in postmenopausal women increases significantly circulating nitrite plus nitrate levels. The effect of estrogen on NO synthesis is rapid and is maintained with repeated administration. We demonstrated the effects of estrogen replacement therapy in Andean postmenopausal women were associated with a significantly increase in plasma levels of nitrite plus nitrate. Our hypothesis is that beneficial effect of estrogen replacement therapy on involutive depression in postmenopausal women is mediated by increase in NO production by central nervous system.

Physiological changes in platelet aggregation and nitric oxide levels during menstrual cycle in healthy women.

Hormonal levels, mainly those of estrogens, protect women from the appearance of cardiovascular diseases by an increasing nitric oxide (NO) activity. NO is an endogenous vasodilator and antiaggregating substance. We decided to investigate platelet function and plasma levels of nitric oxide during preovulatory and midluteal phases in young and healthy women with normal menstrual cycles (MCs). Nine young, healthy female subjects had recorded three consecutive MCs before entering this program. Platelet-rich plasma (PRP) was used for the determination of platelet aggregation and NO measurements. Moreover, platelet sensitivity to the inhibitory effect of exogenous NO was tested. The EC(50) of collagen showed no differences between the preovulatory (1.36+/-0.16 microg/mL) and the midluteal (1.31+/-0.08 microg/mL; P, NS) phases. However, the EC(90) during the preovulatory phase was higher (2.05+/-0.2 microg/mL) than during the midluteal phase (1.8+/-0.6 microg/mL). Plasma levels of NO were lower during the preovulatory phase (19.1+/-2 microM) in comparison to the midluteal phase (20.9+/-2.3 microM). Interestingly, the exogenous amount of NO to produce at least half of the inhibition of an EC(90) collagen-induced aggregation was higher at the preovulatory phase (323.3+/-60.9 nM) than during the midluteal phase (240.0+/-37.5 nM; P, NS). We propose that during the follicular phase platelets rather use NO produced by the endothelium; therefore, it is necessary to add more agonist to activate those, but it results in higher consumption of circulating NO, whereas during luteal-phase platelets are not able to use NO, requiring lower amounts of agonist and thus resulting in higher plasma levels of NO. This is an interesting fact in research on cardiovascular diseases of women.

Intraplatelet Cyclic Guanosine‐3′,5′‐Monophosphate Levels During Pregnancy and Preeclampsia

Objective: To investigate the intraplatelet cyclic guanosine‐3′,5′‐monophosphate (cGMP) levels during normal pregnancy and preeclampsia. Study Design: Pregnant women (n = 15), women with preeclampsia (n = 15), and nonpregnant, normotensive women (n = 15) were included. Intraplatelet cyclic guanosine‐3′,5′‐monophosphate levels were measured by an enzyme‐linked immunosorbent assay. Results: Intraplatelet cGMP levels were significantly different among all groups (p < 0.02). The values were higher in normal pregnant women (mean 19.8 SD 2.6 fmol/105 platelets) in comparison to nonpregnant women (mean 7.6 SD 0.3 fmol/105 platelets; p = 0.001) and women with preeclampsia (mean 11.3 SD 1.8 fmol/105 platelets; p = 0.05). Plasma nitric oxide levels did not reveal differences between all groups. Conclusions: The results of this study in a high‐risk Andean population demonstrated that intraplatelet cyclic guanosine‐3′,5′‐monophosphate levels are decreased during preeclampsia compared to normal pregnancy, suggesting a lack in action of nitric oxide.

Seroprevalence of antibodies to Chlamydia pneumoniae in women with preeclampsia [3] (multiple letters)

I thank Dr. Hurd and his colleagues for their interest in our study regarding the use of postpartum magnesium sulfate seizure prophylaxis in patients with hypertensive diseases of pregnancy. They correctly calculate that a study population of greater than 16,000 patients would be needed to achieve the power necessary to definitively state that a clinically based regimen of seizure prophylaxis administration has the same safety profile as an arbitrary time-based regimen. As my colleagues and I stated in the Discussion section, “the current study raises several points for further investigation” that “lead us to favor a large, multicenter trial to investigate the optimal patient population and duration of postpartum magnesium sulfate.” I believe Drs. Fejgin and Goldberger’s case emphasizes the importance of such a trial, and it is my hope that it will be performed to further clarify the appropriate management of hypertensive diseases of pregnancy.

Plasma and placental nitric oxide levels in women with and without pre-eclampsia living at different altitudes

To investigate the nitric oxide (NO) levels in the plasma and the placentas of pregnant women with pre‐eclampsia and women without pre‐eclampsia, and to determine the effect of high or low altitude of residence.

Abnormal release of nitric oxide from nitrosoprotein in preeclampsia

Preeclampsia (PE) is a common (~7% of all pregnancies) disorder of human pregnancy in which the normal hemodynamic response to pregnancy is compromised. S-nitroso derivatives of protein and non-protein thiols acts like NO. However transition metals and reductants are often required for this function [1]. This study investigates the release of nitric oxide (NO) from plasma S-nitrosoprotein in normal pregnant (NP n = 60) preeclamptic (PE n = 30) and non-pregnant women (NON-P n = 30) attending to Hospital Gineco-Obstetrico Isidro Ayora in Quito Ecuador. (excerpt)