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Biomedical subjects

E Cicinelli

Publications and source records attributed to E Cicinelli.

At least 37 records · Page 2Linked to original sources

Different plasma levels of nitric oxide in arterial and venous blood.

Experimental investigations suggest that a basal release of nitric oxide (NO) occurs in arterial but not in venous endothelium. We therefore decided to compare plasma levels of NO in the arterial and venous circulation. Parallel blood samples were drawn from the radial artery and brachial vein in 15 healthy drug-free women. Nitric oxide levels were assessed by measuring plasma levels of nitrite and nitrate, the two stable oxidation products of NO metabolism. Plasma levels of NO metabolites in arterial blood were significantly higher than in the paired venous blood samples (45.1 +/- 17.7 versus 22.5 +/- 8.5 mumol l-1, respectively, mean +/- SD). The results of this preliminary study strongly suggest that the endothelial release of NO is probably different in arteries and veins in vivo; this is also consistent with previous literature indicating that basal release of NO occurs mainly from the endothelium of arteries but not from that of veins.

Arteries↗

Effects of short-term transdermal estradiol administration on plasma levels of nitric oxide in postmenopausal women.

OBJECTIVE: To assess the effects of short-term transdermal E2 administration on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN: Randomized, placebo-controlled trial. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Twenty-eight healthy postmenopausal women. INTERVENTION(S): Transdermal administration of E2 (100 microg/d) or placebo on days 1 and 4 of a 1-week treatment regimen. MAIN OUTCOME MEASURE(S): Serum concentrations of E2 and plasma concentrations of NO stable oxidation products were assessed on day 1, before placement of the patch, and subsequently on days 2, 3, and 6. RESULT(S): The mean concentration of NO metabolites on days 2, 3, and 6 was significantly greater in the E2 group (40.08+/-15.42 micromol/L, 38.05+/-18.82 micromol/L, and 42.03+/-16.81 micromol/L on days 2, 3, and 6, respectively) compared with both baseline levels (23.07+/-5.79 micromol/L) and the placebo group (23.51+/-4.06 micromol/L, 21.64+/-4.72 micromol/L, and 21.81+/-4.46 micromol/L on days 2, 3, and 6, respectively). CONCLUSION(S): During a 1-week treatment regimen with transdermal E2, plasma levels of NO in postmenopausal women were significantly higher than baseline levels on days 2, 3, and 6. This suggests that the effect of estrogens on NO synthesis is rapid and that it is maintained with repeated administration.

Administration, Cutaneous↗

Plasma concentrations of progesterone are higher in the uterine artery than in the radial artery after vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women.

OBJECTIVE: To verify the occurrence of preferential distribution of vaginally administered progesterone to the uterus compared with extrapelvic regions in vivo and in humans. DESIGN: Prospective clinical study. SETTING: University medical school. PATIENT(S): Twenty postmenopausal women undergoing transabdominal hysterectomy for benign pathologies. INTERVENTION(S): Forty-five minutes before surgery, the women received a single vaginal administration of an oil-based micronized progesterone (100 mg) solution currently available on the market for IM use. During the operation, parallel blood samples were drawn from the uterine and radial arteries. MAIN OUTCOME MEASURE(S): Plasma levels of progesterone were measured by RIA. RESULT(S): Mean (+/- SD) plasma levels of progesterone were significantly higher in the uterine artery than in the radial artery (9.75 +/- 3.21 vs. 5.12 +/- 2.06 ng/mL, respectively). CONCLUSION(S): Vaginal administration allows a preferential distribution of progesterone to the uterus, which confirms the existence of the so-called "first uterine pass effect."

Administration, Intravaginal↗

Paracervical anesthesia for hysteroscopy and endometrial biopsy in postmenopausal women. A randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficiency of paracervical anesthesia in reducing pain and the incidence of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women. STUDY DESIGN: A randomized, placebo-controlled, double-blind study. Seventy-two postmenopausal women underwent diagnostic hysteroscopy and endometrial biopsy. Hysteroscopies were performed by using a lens-based endoscope with a diameter of < 4 mm and endometrial biopsies by using a 3-mm Novak's curette. Ten milliliters of 1.5 mepivacaine or saline solution was injected at the junction of the cervix and vagina (at the 4 and 8 o'clock positions) by means of an appropriate needle before performing the intrauterine procedures. Referred pain was evaluated by means of a visual analogue scale; continuous monitoring of heart rate and blood pressure was also performed. RESULTS: Paracervical anesthesia significantly reduced pain at hysteroscopy and biopsy. The incidence of vasovagal reactions was also significantly lower in the anesthetized group. CONCLUSION: Paracervical anesthesia is effective for hysteroscopy and endometrial biopsy in postmenopausal women and may be indicated particularly for patients with cervical stenosis, for very anxious subjects and in all situations where pain stimulation could trigger threatening side effects due to systemic pathologies.

Anesthesia, Local↗

Acute effects of transdermal estradiol administration on plasma levels of nitric oxide in postmenopausal women.

OBJECTIVE: To investigate the acute effects of transdermal E2 administration on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN: Randomized, placebo-controlled trial. SETTING: Normal human volunteers in an academic research environment. PATIENT(S): Twenty healthy postmenopausal women. INTERVENTION(S): Transdermal administration of 100 micrograms/d E2 or placebo. MAIN OUTCOME MEASURE(S): Plasma concentrations of NO stable oxidation products and serum concentrations of E2 were assessed before and 24 hours after the administration. RESULT(S): In the group treated with E2 mean concentration of NO metabolites 24 hours after patch application (37.31 +/- 7.62 mumol/L) resulted significantly higher than baseline (21.04 +/- 5.71 mumol/L) and the control group (23.50 +/- 4.03 mumol/L). The correlation between the mean percent increase in NO metabolites and absolute E2 concentrations 24 hours after the E2 administration was statistically significant. CONCLUSION(S): Transdermal administration of E2 to healthy postmenopausal women increases the plasma levels of NO and this supports the hypothesis that a NO-related mechanisms may contribute to the cardiovascular protective effect of estrogens in postmenopause.

Administration, Cutaneous↗

Propofol assay in biological fluids in pregnant women.

A rapid, accurate and sensitive UV derivative method was described for measuring the Propofol concentration in some biological fluids. Furthermore two alternative procedures, a gaschromatographic and a colorimetric, were also defined, and the results of the three methods, when applied on blood samples spiked with known amounts of analyte, were compared. The samples were preliminary purified by a solid phase extraction on octadecyl C18 cartridge. The UV derivative method was applied to a pharmacokinetic study on pregnant women undergoing cesarean sections. After an induction dose administration of 2.5 mg kg-1, the maternal and umbilical vein blood were found to have comparable concentrations of propofol, with a mean half like of about 3.5 min; on the contrary no detectable levels of the drug were found in amniotic fluid. The drug recoveries > 98% and the response was linear over the range 0.05-40 micrograms ml-1.

Amniotic Fluid↗

Topical anaesthesia for diagnostic hysteroscopy and endometrial biopsy in postmenopausal women: a randomised placebo-controlled double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of topical anaesthesia in reducing pain and incidence of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women. DESIGN: Randomised placebo-controlled double-blind study. SETTING: University hospital. PARTICIPANTS: Eighty postmenopausal women undergoing diagnostic hysteroscopy and endometrial biopsy. INTERVENTIONS: Two millilitres of 2% mepivacaine or saline solution were injected transcervically into the uterine cavity before performing the procedures. MAIN OUTCOME MEASURES: Evaluation of pain reduction on a visual analogue scale and continuous monitoring of heart rate and blood pressure. RESULTS: The use of the anaesthetic significantly reduced the pain experienced at hysteroscopy and endometrial biopsy. The occurrence of vasovagal reactions was significantly lower in the anaesthetised group. CONCLUSIONS: Topical anaesthesia attenuated pain and effectively prevented the occurrence of vasovagal reactions during hysteroscopy and endometrial biopsy in postmenopausal women.

Anesthetics, Local↗

Effects of continuous percutaneous estradiol administration on skeletal turnover in postmenopausal women: a 1-year prospective controlled study.

The aim of this study was to investigate the short and long term effects of continuous percutaneous administration of estradiol (E2) cream on skeletal turnover in women in surgical postmenopause. Forty women were randomly divided into two groups, one treated with a single daily application of 3 mg/day E2 cream continuously for 12 months, the other receiving placebo cream. Forearm densitometry was performed before and at the end of treatment. Serum E2, osteocalcin (BGP), alkaline posphatase (AP) and urinary N-telopeptide of type I collagen (NTX) were also measured at baseline, month 4 and 12 of the protocol. At month 4, bone turnover was also assessed by evaluating 99mtechnetium-methylene diphosphonate (99mTc-MDP) skeletal uptake. Changes in E2, BGP, AP and NTX as well as 99mTc-MDP skeletal uptake in hormone group vs. placebo were significant after 4 months of treatment. At month 12, proximal site densitometry showed no variation in either group whereas the percentage of variation in distal site measurements resulted significantly different with an increase in the hormone group and a reduction in the placebo group. In conclusion continuous percutaneous administration of E2 cream was effective in rapidly reducing bone turnover in postmenopausal women and in counteracting the accelerated postmenopausal bone loss.

Absorptiometry, Photon↗

Pharmacokinetics and endometrial effects of the vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women.

OBJECTIVE: To study the pharmacokinetics of the transvaginal absorption of 100 mg micronized P from an oil-based solution in postmenopausal women before and after the estrogenization of the vaginal mucosa and to evaluate the endometrial effects of 10 days of once daily P vaginal administration. DESIGN: Prospective clinical trial. SETTING: University Medical School. PATIENTS: Nine postmenopausal women undergoing hormone replacement therapy. INTERVENTIONS: A micronized P (100 mg) oil-based solution currently available on the market for IM use was administered vaginally by means of a Teflon cannula without the aid of a speculum. Subsequently, the women received 4 weeks 0.1 mg/d transdermal E2 treatment combined on the last 10 days with the once daily vaginal administration of P in the same way as before. MAIN OUTCOME MEASURES: At the first (before estrogen) and second (during estrogen therapy) P administrations, P serum levels were measured at time 0, and then after 15, 30, 45, 60, 120, 240, 480, and 1440 minutes. Endometrial samples were collected at the end of treatment. RESULTS: After the first administration, a mean Cmax of 5.40 +/- 0.92 ng/mL (mean +/- SD) was reached at a Tmax of 45 minutes (range 30 to 480 minutes). The serum concentrations returned to their initial values after 24 hours. The second P administration reached a mean Cmax of 5.30 +/- 1.04 ng/mL at a Tmax of 60 minutes (range 30 to 240 minutes); after 24 hours, the serum P levels still were significantly higher than at baseline and at the same time after the first administration. None of the women complained of significant vaginal losses. No signs of vaginal phlogosis or irritation were observed. In all subjects, histologic evaluation showed clear endometrial secretory changes. CONCLUSIONS: The daily vaginal administration of one vial of micronized P for 10 days allowed useful serum P levels to be reached, especially after estrogen therapy, and induced clear secretory changes in the endometrium.

Administration, Cutaneous↗

Circulating levels of nitric oxide in fertile women in relation to the menstrual cycle.

OBJECTIVE: To investigate nitric oxide (NO) production in the two phases of normal menstrual cycle. DESIGN: Prospective clinical study. SETTING: Normal human volunteers in an academic research environment. PATIENT(S): Fifteen normally cycling women. INTERVENTION(S): Follicle growth monitoring by ultrasound, serum, and plasma sampling in the midfollicular phase, at ovulation, and in the midsecretory phase. MAIN OUTCOME MEASURE(S): Plasma concentration of NO stable oxidation products and serum concentrations of E2 and P. RESULT(S): Plasma concentration of NO metabolites resulted higher in the follicular phase with respect to the secretory phase and peaked at midcycle. CONCLUSION(S): The results strongly support the existence of an E2 control of NO production and release. The significant reduction in NO metabolites observed in the secretory phase suggests a possible opposing action of P on either NO production or release.

Adult↗

Topical anesthesia for hysteroscopy in postmenopausal women.

STUDY OBJECTIVE: To evaluate the efficacy and safety of topical anesthesia in reducing pain and the frequency of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: A university hospital. PATIENTS: Forty-two postmenopausal women undergoing diagnostic hysteroscopy and endometrial biopsy. INTERVENTIONS: Two milliliters of 2% mepivacaine or saline solution was injected transcervically into the uterine cavity before performing the procedures. MEASUREMENTS AND MAIN RESULTS: Pain was evaluated on a visual analog scale, and heart rate and blood pressure were monitored continuously. Anesthesia reduced the pain experienced at hysteroscopy and endometrial biopsy, but not significantly. The frequency of vasovagal reactions was significantly lower in the anesthetized group. CONCLUSIONS: Topical anesthesia effectively prevents the occurrence of vasovagal reactions in postmenopausal women undergoing hysteroscopy and endometrial biopsy.

Anesthesia, Local↗

Nasal spray bromocriptine: effects on serum prolactin in puerperal women.

BACKGROUND: The objective of this study was to investigate the effectiveness of a single nasal spray administration of 0.8 mg bromocriptine in reducing PRL serum levels. METHODS: Eighteen physiologically hyperprolactemic women in the early days of puerperium were randomized to receive nasal bromocriptine or placebo; PRL serum levels were measured by RIA at 45, 30 and 15 minutes before the administration and after the following times: 15, 30, 45, 60, 120, 180, 240, 300, and 480 minutes. RESULTS: After the administration of bromocriptine serum levels of PRL decreased rapidly; the reduction was statistically significant after 45 minutes. Four hours after the administration mean serum levels of PRL resulted in the normal range (< 20 micrograms/l); at the eighth hour the PRL levels were still normal. No one patient complained of any local or systemic side-effects. CONCLUSION: Nasal route seems to be an effective and probably safe administration route for bromocriptine.

Aerosols↗

Nasal spray administration of bromocriptine: pharmacology and effect on serum prolactin level in puerperal women.

This study was aimed at investigating the absorption of nasally administered bromocriptine and its effect on serum prolactin level. Fifteen physiologically hyperprolactinemia women who had asked to discontinue breast feeding received a single nasal spray administration of 0.8 mg bromocriptine. Serum prolactin levels were measured by radioimmunoassay at 30 and 15 min before drug administration, at the time of administration and at 15, 30, 60, 120, 240, 480 and 720 min after administration; bromocriptine was radioimmunoassayed in only five of the patients from time 0 to 720 min after administration. Serum bromocriptine levels increased rapidly after administration, reached a maximum at 120 min and thereafter declined slowly over the subsequent 10 h. As the bromocriptine level increased there was a decline in the serum prolactin level. The first significant decline in serum prolactin level compared with the baseline level occurred at 30 min after administration and the level continued to decrease significantly until time 120 min. Four hours after administration the mean serum prolactin level was within the normal assay range. The maximum decline in serum prolactin level was reached at 720 min after administration. Correlation analysis between serum bromocriptine and prolactin concentrations yielded a significant negative value between times 0 and 120 min after administration. There was no significant change in mean orthostatic systolic or diastolic blood pressure or in mean heart rate. Only one patient complained of headache and dizziness; another experienced mild transient nausea, and none had vomiting. Ten patients (66.67%) reported light endonasal burning and an unpleasant taste which subsided after a few minutes; no patient showed nasal irritation at nasal examination. In conclusion, nasal administration of 0.8 mg bromocriptine was effective in reducing the serum prolactin level for more than 12 h after administration without inducing significant side-effects.

Administration, Intranasal↗

Transabdominal sonohysterography, transvaginal sonography, and hysteroscopy in the evaluation of submucous myomas.

OBJECTIVE: To assess the usefulness of transabdominal sonohysterography in the diagnosis and evaluation of submucous myomas. METHODS: Fifty-two premenopausal women hospitalized for hysterectomy for benign gynecologic indications underwent preoperative conventional transvaginal sonography, transabdominal sonohysterography, and hysteroscopy. The results of the three techniques in terms of diagnosis, size, intracavitary growth, and location of the submucous myomas were compared with those revealed by direct inspection of the surgical specimens. RESULTS: Conventional transvaginal sonography for the diagnosis of submucous myomas had a sensitivity of 90% and a specificity of 98%; the predictive values of abnormal and normal scans were 90 and 98%, respectively. Transabdominal sonohysterography had sensitivity, specificity, and predictive values of 100%, as did hysteroscopy. In all cases, the sonographic techniques measured tumor size more accurately than did hysteroscopy. The transabdominal sonohysterography measurements differed from direct evaluation by no more than 2 mm, and the hysteroscopic measurements were significantly different from those of the surgical specimens. The sonohysterographic evaluation of intrauterine growth was significantly more precise than that of the other techniques, differing from direct measurements by no more than 5-10%. Conventional transvaginal sonography failed to localize three of 11 myomas; hysteroscopy and transabdominal sonohysterography provided the exact location in all cases. CONCLUSION: Transabdominal sonohysterography is the most accurate technique for detecting submucous myomas and evaluating their size, intracavitary growth, and location.

Abdomen↗

Administration of unmodified progesterone by nasal spray in fertile women.

A 11.20-mg dose of progesterone was administered by nasal spray to five healthy fertile women in the follicular phase of the menstrual cycle. Serial blood samples were collected and Cmax (the maximum progesterone concentration reached), Tmax (the time at which Cmax was reached) and the area under the curve (AUC), with the time limits of 0 and 720 min, were calculated. Serum progesterone levels were assayed by means of a non-extraction [125I]radioimmunoassay. The mean Cmax was 4.50 +/- 2.31 ng/ml at a Tmax of 30 min; levels returned to baseline after 720 min. The mean AUC value was 1180.50 +/- 613.90 ng.h/ml. The progesterone administered by nasal spray in fertile women was effective in reaching physiological progesterone levels. Even if a nasal first-pass metabolic effect is taken into account, this route allows progesterone to avoid liver first-pass metabolism and its metabolic consequences.

Administration, Intranasal↗

[Transvaginal absorption of an oleic solution of progesterone (Gestone) in fertile women].

Transvaginal absorption of a progesterone (P) oleic formulation, commercially available for intramuscular administration (Gestone, Amsa, Rome), has been investigated in five fertile women in the follicular phase. The contents of a vial, corresponding to P 100 mg, was administered intravaginally by a syringe connected to an atraumatic cannula inserted in the vagina. While administering and for a further 10 minutes the woman remained in the recumbent position. Blood samples for P assay were drawn at the following times: 0, 15, 30, 45, 60, 120, 240, 360, 480 and 1440 minutes. Mean CMax was 5.08 +/- 1.66 ng/ml, and the difference between baseline and CMax values was statistically significant (p < 0.01). TMax resulted as 60 minutes (range 45-240 minutes). Mean serum levels lowered subsequently but resulted as still significantly higher than baseline (p < 0.05) after 1440 minutes. Mean AUC 0-1440 value was 4236.75 ng h/ml. Any local or systemic side-effects were noted. No evidence of vaginal irritation was observed in any women. On the basis of the present data it is possible to suggest that a twice daily administration schedule could ensure suitable P serum levels in fertile women.

Adult↗