Resolution of subchorionic hematoma and symptoms of threatened miscarriage using vaginal alpha lipoic acid or progesterone: clinical evidences.

OBJECTIVE: Alpha Lipoic Acid (ALA) is a safe natural molecule that exerts a selective immunomodulating activity with antioxidant and anti-inflammatory properties. This randomized controlled clinical trial (RCT) tested the effect of the vaginal administration with ALA or Progesterone, in subchorionic hematoma resorption in women with threatened miscarriage. PATIENTS AND METHODS: 400 mg of vaginal Progesterone or 10 mg of vaginal ALA were administered to sixty-two pregnant women, in the first trimester of gestation with threatened miscarriage and subchorionic hematoma. Controls were patients who chose not to receive any treatment. RESULTS: In the ALA group the subchorionic hematoma was reabsorbed more quickly in comparison with the progression detected in Progesterone group (p ≤ 0.05). The other parameters checked (pelvic pain and vaginal bleeding) did not show any significant difference and a smaller number of miscarriages was recorded in the ALA group, compared to Progesterone group. CONCLUSIONS: Our data provides the first evidence of the efficacy of ALA, administered by vaginal route, in the healing process of patients with threatened miscarriage, thus supporting the normal course of pregnancy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02601898 (ClinicalTrials.gov registry).

[Counseling about folate intake during pregnancy]. / Counseling per l'utilizzo di folati nella gravidanza.

AIM: In gynecology, the importance of an adequate folate intake in the periconceptional period and during pregnancy is widely accepted. Its purpose is to decrease the risk of maternal and fetal diseases, such as neural tube defects (NTD), so that Italy strongly recommends that women who are pregnant or are planning to become pregnant receive folate supplementation (i.e. 0.4 or 4-5 mg per day, as needed). Despite that, recent studies show women's low awareness of the importance of folate supplementation, above all during the periconceptional period. Basing on these considerations, we surveyed pregnant women to investigate their awareness and the real use of folate. METHODS: From January to October 2014 we surveyed 650 pregnant women. We used a questionnaire with closed and semi-closed questions. RESULTS: The mean age of the enrolled women was 32.8 (±2.9). The survey showed that a significant proportion of women knew folate benefits in pregnancy (about 70%) and they used it during gestational period (89.8%), whereas folate supplementation during periconceptional period was inadequate, used by only the 16.9% of women and often at a lower than recommended amount. CONCLUSION: Awareness and use of folate can be promoted through informational campaigns among general practitioners and obstetricians/gynecologists, through preconceptional and prenatal counseling, and through a risk assessment addressed to choose the appropriate folate type and dosage.

[Use of alpha-lipoic acid and omega-3 in postpartum pain treatment]. / [Acido alfa-lipoico e omega-3 nel trattamento del dolore nel postpartum.

Postpartum pain is a frequent condition that negatively affects women's quality of life, interferring with everyday life. Analgesic drugs and surgery are often contraindicated in pregnancy and during breast feeding. This review of the literature aims to evaluate the rational of the association of lipoic acid and omega-3 employ in the management of postpartum pain. Lipoic acid is a cofactor essential in mitochondrial metabolism with antioxidant and anti-inflammatory activity. Lipoic acid has been shown to be effective in neuropatic pain treatment in patients with sciatica, carpal tunnel syndrome and diabetic neuropathy. Omega-3 are known for their anti-inflammatory and neurotrophic activity. The peripheral and central activity of both substances allows to act on neuroinflammation mechanisms thus reducing cronicization of pain and also determining a potential improvement of women's emotional status. The preliminary data here presented confirm the positive effect of this association on the treatment of postpartum perineal pain. The supplementation of lipoic acid in association with omega-3 seems effective and safe for the treatment of chronic postpartum pain, allowing a pathogenetic approach to neuroinflammation, thus reducing the consumption of analgesic drugs, often contraindicated during breast-feeding.

Hyaluronic acid and vitamins are effective in reducing vaginal atrophy in women receiving radiotherapy.

AIM: During the last decades, therapies targeting cervical cancer have been considerably improved. Surgery and radiotherapy (RT) represent the main common therapeutic approach in cervical cancer. In order to minimize the side effects of radiotherapy approach, several protocols have been developed such as brachytherapy (BRT). Among the side effects associated with RT, the vaginal atrophy is the most important and common one. Vaginal atrophy, in turn, leads to additional alterations like inflammation, associated to relevant symptoms such as itching, burning and dyspareunia. All these alterations heavily affect the quality of women's life. The aim of our study was to evaluate the toxicity induced by RT on vaginal mucosa, and the adjuvant action of a product containing LMWHA, vitamin A, and Vitamin E (Santes®, Lo.Li. Pharma, Rome, Italy). The introduction of adjuvant therapies may have likely had a relevant place in providing that result. METHODS: A prospective randomized study was designed. From October 2006 to October 2008, 45 women with a mean age 38 ± 6 years were enrolled. After surgery, all patients were treated with 4 weeks of RT and 4 weeks of BRT, concomitantly with chemiotherapy. They were randomly assigned in two groups: 23 women were treated with two suppositories (Santes®) per day for 4 months. For the first two months the preventive treatment was simultaneous to RT and BRT. Instead the control groups for composed by 22 patients and they did not undergo any treatment during RT. To evaluate the efficacy of Santes® treatment three biopsies were performed. RESULTS: At the second biopsy, after the BRT therapy, the treated group showed a statistically significant improvement (P<0.05 vs. control) on inflammation, cell atypia, fibrosis, mucositis and bleeding. At the third biopsy, two months after BRT, further statistically improvement were observed for all RT/BRT associated side effects. The treatment showed an efficacy also in terms of pain severity. CONCLUSION: Our data suggest that low molecular weight HA shows good performances in treating RT-damaged tissue and plays a key role in all steps of the healing process. Indeed the results shows that women exposed to RT treatments and simultaneously treated with Santes®, had an optimal resolution of vaginal atrophy and related symptoms.

Peripheral neuropathy in obstetrics: efficacy and safety of α-lipoic acid supplementation.

OBJECTIVE: Neuropathic pain during pregnancy is a common condition due to the physical changes and compression around pregnancy and childbirth that make pregnant women more prone to develop several medical conditions such as carpal tunnel syndrome, sciatica, meralgia paraesthetica and other nerve entrapment syndromes. Most of the treatments usually performed to counteract neuropathic pain are contraindicated in pregnancy so that, the management of these highly invalidating conditions remains an issue in the clinical practice. We aimed to review the efficacy and safety of alpha lipoic acid supplementation in the treatment of neuropathic pain. DISCUSSION: Lipoic acid is a co-factor essential in the regulation of mitochondrial energy. It has been demonstrated that lipoic acid supplementation is involved in several biochemical processes and actions, exerting important antioxidant and anti-inflammatory activity and significantly improving pain and paraesthesia in patients with sciatica, carpal tunnel syndrome and diabetic neuropathy. CONCLUSIONS: Efficacy of lipoic acid is combined with a high safety profile, making this molecule a novel candidate for the management of several diseases. Data reported so far are promising and dietary supplementation with lipoic acid seems a useful tool to contrast neuropathic pain during pregnancy.

[Role of D-chiro-inositol in glucidic metabolism alterations during pregnancy]. / Ruolo del D-chiro inositolo nelle alterazioni del metabolismo glucidico in gravidanza.

The recent epidemiological explosion of diabetes amplified the problems regarding the various complications related to the disease and its complex healthcare management. Among these, those relating to the pregnancy of women with diabetes are highly significant from the point of view of social health, for the consequences of the disease on the unborn child, but also in the mother. It is possible that diabetes exists before pregnancy (pregestational diabetes), but much more often it can appear during pregnancy in women unaware of the disease (gestational diabetes). The mainstay of therapy for diabetes and gestational diabetes resides in diet, therapy with oral hypoglycemic agents or insulin, but the appearance on the market of supplements consisting of substances such as D-chiro-Inositol (DCI) arousing considerable interest, as it seems to be able to help in the glycemic control in this type of disease but, of course, its effectiveness must be proved. The data of our study seem to show that the DCI supplement has a role in the regulation of glucose metabolism and insulin sensitivity, and is able to act on the metabolism of pregnant women at risk of developing gestational diabetes, who probably have a basic alteration of insulin and glucose metabolism. It acts improving insulin sensitivity and reducing the onset of gestational diabetes in pregnant women at risk, decreasing the weight gain and nocturnal hypoglycemia responsible for the attacks of hunger at night. Further studies would be desirable to clarify the mechanism of action of DCI at the cellular level in glucose metabolism during pregnancy, and clinical data must be confirmed with wider studies.

Low-velocity granular drag in reduced gravity.

We probe the dependence of the low-velocity drag force in granular materials on the effective gravitational acceleration (g(eff)) through studies of spherical granular materials saturated within fluids of varying density. We vary g(eff) by a factor of 20, and we find that the granular drag is proportional to g(eff), i.e. that the granular drag, F(probe), on a vertical cylinder follows the expected relation F(probe)=ηρ(grain)g(eff)d(probe)h(probe)(2) where the drag is related to the probe's depth of insertion, h(probe); the probe's diameter, d(probe); the grain material's density, ρ(grain); and a dimensionless constant, η. The dimensionless constant shows no systematic variation over four orders of magnitude in effective grain weight, demonstrating that the relation holds over that entire range to within the precision of our data.

Valproate-induced delirium in a demented patient.

In this study we report a case of valproate-induced delirium in a patient affected with Alzheimer's disease (AD). A 75-year-old woman with AD presented moderate cognitive impairment associated to behavioral disorders, characterized by aggression, agitation, severe insomnia. She was treated with galantamine, promazine, acetylsalicylic acid and pantoprazole. Since behavioral disorders worsened more and more, home neurological consultation was asked. The neurologist prescribed a mood stabilizer, sodium valproate 500 mg daily for the first week and then, twice a day and stopped promazine. After an apparent initial benefit, about 16 days later, patient suddenly developed hyperactive delirium. It was characterized by worsening of insomnia and agitation, severe confusion, delusions, visual hallucinations alternated to sedation. She became progressively unable to walk and completely dependent in daily living activities. An urgent geriatric consultation was performed at patient's home; physical examination showed mild dehydration, normal blood pressure. Oxygen saturation and electrocardiogram were normal. Sodium valproate was immediately stopped and rehydration was performed. The patient was admitted to a Geriatric Unit, where organic and metabolic damages were excluded. During the hospital stay the patient was agitated, aggressive, confused; intramuscular haloperidol 5mg and saline intravenous infusion 1500 cc daily were performed, they were partly successful. Three days after she was discharged and continued treatment with oral haloperidol 5mg daily. One week later the patient recovered and she is at present healthy. This is a case report of valproate-induced delirium. The Naranjo scale scored 7, classifying this drug-related event as probable. The present case report suggests the need for minimizing the use of psychoactive drugs in elderly demented patients, whether possible; age-related changes in pharmacokinetics and pharmacodynamics suggest the opportunity of a careful evaluation and a slow titration of treatments in these patients.

Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial.

To investigate the effects of treatment with Myo-inositol (an insulin sensitizing drug), on circulating insulin, glucose tolerance, ovulation and serum androgens concentrations in women with the Polycystic Ovary Syndrome (PCOS). Forty-two women with PCOS were treated in a double-blind trial with Myo-inositol plus folic acid or folic acid alone as placebo. In the group treated with Myo-inositol the serum total testosterone decreased from 99.5 +/- 7 to 34.8 +/- 4.3 ng/dl (placebo group: from 116.8 +/- 15 to 109 +/- 7.5 ng/dl; P = 0.003), and serum free testosterone from 0.85 +/- 0.1 to 0.24 +/- 0.33 ng/dl (placebo group: from 0.89 +/- 0.12 to 0.85 +/- 0.13 ng/dl; P = 0.01). Plasma triglycerides decreased from 195 +/- 20 to 95 +/- 17 mg/dl (placebo group: from 166 +/- 21 to 148 +/- 19 mg/dl; P = 0.001). Systolic blood pressure decreased from 131 +/- 2 to 127 +/- 2 mmHg (placebo group: from 128 +/- 1 to 130 +/-1 mmHg; P = 0.002). Diastolic blood pressure decreased from 88 +/- 1 to 82 +/- 3 mmHg (placebo group: from 86 +/- 1 to 90 +/- 1 mmHg; P = 0.001). The area under the plasma insulin curve after oral administration of glucose decreased from 8.54 +/- 1.149 to 5.535 +/- 1.792 microU/ml/min (placebo group: from 8.903 +/- 1.276 to 9.1 +/- 1.162 microU/ml/min; P = 0.03). The index of composite whole body insulin sensitivity (ISI comp) increased from 2.80 +/- 0.35 to 5.05 +/- 0.59 mg(-2)/dl(-2) (placebo group: from 3.23 +/- 0.48 to 2.81 +/- 0.54 mg(-2)/dl(-2); P < 0.002). 16 out of 23 women of Myo-inositol group ovulated (4 out of 19 in placebo group). Treatment of PCOS patients with Myo-inositol provided a decreasing of circulating insulin and serum total testosterone as well as an improvement in metabolic factors.

Starting to move through a granular medium.

We explore the process of initiating motion through a granular medium by measuring the force required to push a flat circular plate upward from underneath the medium. In contrast with previous measurements of the drag and penetration forces, which were conducted during steady state motion, the initiation force has a robust dependence on the diameter of the grains in the medium. We attribute this dependence to the requirement for local dilation of the grains around the circumference of the plate, as evidenced by an observed linear dependence of the initiation force on the plate diameter.

[Preliminary evaluation of a vaginal cream containing lactoferrin in the treatment of vulvovaginal candidosis]. / Studio preliminare sull'utilizzo di una crema contenente Lattoferrina nel trattamento della vulvovaginite acuta da candida.

AIM: The objective of the study is to verify the clinical effectiveness of a cream containing lactoferrin in the treatment of acute vulvovagininal candidiasis. METHODS: The study enrolled 34 patients aged 25-45 years and preenting signs and symptoms of acute vulvovaginal candidiasis. The patients have been treated with a cream containing lactoferrin 4%, 5 g of cream in vagina and 2 cm applied on the vulva twice a day for 7 days. At the end of the treatment the patients a clinical and microscopical examination was performed in order to evaluate the effectiveness of the therapy. RESULTS: The results obtained showed that 27 women completely recovered, 5 showed a good improvement and only 2 women were still suffering from vulvovaginitis at the end of treatment. CONCLUSION: From the data of our study, a cream containing lactoferrin seems to be clinically effective in the treatment of acute vulvovaginal candidiasis, with a good response on all the characteristic symptoms of this infection.

Effectiveness and safety of vaginal suppositories for the treatment of the vaginal atrophy in postmenopausal women: an open, non-controlled clinical trial.

Menopause, due to the physiological decrease in the estrogens levels, is often associated with many symptoms related to vaginal atrophy such vaginal dryness, dyspareunia, burning, itching, decreasing in libido and therefore a worsening of the quality of life and in particular of the sexual activity. There are many pharmacological remedies to solve these events, first of all hormone replacement therapy (HRT) that up to the 90s was the therapy of choice for the care of the menopause symptoms. This hormonal therapy, however, has been re-considered due to its side effects. As alternative, a clinical trial has been performed to investigate the efficacy and safety, in postmenopausal women with urogenital atrophy, of the use of suppositories for vaginal use, containing hyaluronic acid, vitamin E and vitamin A. The trial, according to a open, non-controlled design, was performed on 150 postmenopausal women, 1 vaginal suppository per day, for the first 14 days and then a vaginal suppository, day in and day out, for other 14 days. The primary endpoint was the evaluation of vaginal dryness assessed by a Visual Analogue Scale (VAS) both by the investigator and the patient. The secondary endpoints were the evaluation of all the other symptoms and signs associated with the vaginal atrophy (itching, burning, dyspareunia, vaginal inflammation or swelling, irritation, assessed by a 4-point scale, presence of vaginal abrasions and irritation), and the recording of the adverse events occurring during the trial. The patients have not reported adverse effects during the treatment, and the results in terms of effectiveness on the vaginal atrophy symptoms were markedly positive. A high level of compliance was registered. The product tested can therefore be considered a safe and effective alternative for the treatment of vaginal atrophy symptoms in postmenopausal women, especially when HRT is not recommended.

Analyzing the radiation of the proenkephalin gene in tetrapods: cloning of a Bombina orientalis proenkephalin cDNA.

Analyzing the Radiation of the Proenkephalin Gene in Tetrapods: Cloning of a Bombina orientalis Proenkephalin cDNA: A proenkephalin cDNA was cloned from the brain of the anuran amphibian, Bombina orientalis (Family: Discoglossidae). This cDNA is 1358 nucleotides in length, and contains an open reading frame that codes for 251 amino acids. Within the open reading frame there are seven opioid (YGGF) sequences. There were five Met-enkephalin (YGGFM) sequences that are flanked by sets of paired basic amino acid proteolytic cleavage sites and two C-terminally extended Met-enkephalin sequences: YGGFMRGY and YGGFMRF. No Leu-enkephalin sequences were found in B. orientalis proenkephalin. It was possible to align the amino acid sequences of proenkephalin from several vertebrate taxa (human, Australian lungfish, B. orientalis, Xenopus laevis, Spea multiplicatus) by inserting a minimum of nine gaps. This alignment was then used to analyze the corresponding nucleotides for each proenkephalin sequence using maximum likelihood. This analysis yielded a single tree. In this tree, the Australian lungfish sequence was the outgroup or the tetrapod ingroup. The amphibian sequences form a clade separate from the human sequence. The bootstrap value for the amphibian clade was 100%. Within the amphibian clade the Bombina sequence was the sister group to a clade composed of the X. laevis and S. multiplicatus sequences. The bootstrap value for the X. laevis/S. multiplicatus clade was 94%. Collectively, these data indicate that the sequence of Bombina proenkephalin may be more similar to the proposed ancestral anuran proenkephalin sequence, than either X. laevis or S. multiplicatus proenkephalin.

Activation of the human aldehyde oxidase (hAOX1) promoter by tandem cooperative Sp1/Sp3 binding sites: identification of complex architecture in the hAOX upstream DNA that includes a proximal promoter, distal activation sites, and a silencer element.

Aldehyde oxidase (AOX) is a member of the molybdenum iron-sulfur flavoproteins and is of interest for its role in clinical drug metabolism and as a source of reactive oxygen species (ROS) potentially involved in human pathology. The ROS derived from AOX contribute significantly to alcohol-induced hepatotoxicity. Therefore, expression of AOX could determine both the susceptibility of certain cells and tissues to clinically important pharmacologic agents and the levels of ROS produced under certain pathophysiological conditions. Although some pharmacologic agents regulate AOX enzyme activity, very little is known about the activation or regulation of the human AOX gene (hAOX). In the present study, we sought to identify features in the upstream DNA of hAOX that could confer regulation of the gene, to locate and characterize the basal promoter apparatus activating hAOX, and to identify transcription factors that could mediate activation or regulation. We transfected promoter fusion constructs into epithelial cells from the lung and the mammary gland that express AOX in cell culture. The hAOX gene was found to possess a structurally complex region in the upstream DNA that contained sequences for a proximal promoter, enhancer sites, and silencer elements. In addition, we identified an essential role for the transcription factors Sp1 and Sp3 in the proximal promoter. Unexpectedly, hAOX was activated in lung and mammary epithelial cells by indistinguishable mechanisms. These observations reveal a potentially complex mode of hAOX gene expression in epithelial cells that is dependent on Spl and Sp3 transcription factors.

Use of recombinant hemoglobin solution in reversing lethal hemorrhagic hypovolemic oxygen debt shock.

OBJECTIVE: To compare recombinant hemoglobin solution (rHb1.1) with colloid/blood (CB) resuscitation in a hemorrhagic shock (HS) model based on oxygen debt (O2D). METHODS: Twenty-two anesthetized canines (weight 23.3 +/- 0.2 kg) were bled to an O2D of 99.9 +/- 2.1 mL/kg over 60 minutes (estimated lethal dose 31%), blood loss 65.9 +/- 2.3% of estimated blood volume, - 199 g hemoglobin (Hgb). Prospectively randomized resuscitation done in 20 minutes with 120% of shed blood volume, either colloid 60%/blood 60% shed blood volume (CB), 118 g Hgb, or 120% shed blood volume as 5% rHb1.1, 85 g Hgb, and fall in O2D was quantified over 80 minutes. Six animals died during HS, one after CB resuscitation (32% actual mortality). Blood lactate (L) and base deficit (BEA) were related to O2D. RESULTS: Both lactate (L) and BEA quantified O2D during hemorrhage: L = 0.0671 (O2D) + 1.209; r2 = 0.90, p < 0.0001; BEA = 0.1313 (O2D) + 1.764; r2 = 0.90, p < 0.0001, but L was a better indicator than BEA of fall in O2D during resuscitation (L = 0.069 (O2D) + 1.083; r2 = 0.80). Both groups were followed for 7 days after HS and had normal renal and hepatic function by day 7. However, at equal resuscitation volume, rHb1.1 resuscitation with 41% of Hgb loss produced a more rapid initial fall in O2D than CB at 60% of Hgb loss (p < 0.002). rHb1.1 resuscitation also caused a more complete washout of metabolic acids than CB. CONCLUSIONS: Lactate and BEA accurately quantify O2D in HS and resuscitation. rHb1.1 replacement is as good as CB with regard to survival, but leads to a more uniform reperfusion and produces a more complete resolution of ischemic acidosis.

[Complex extravascular dislocation of a guidewire during catheterization of the subclavian vein]. / Dislocazione complessa extravascolare della guida metallica in corso di cateterizzazione della vena succlavia.

A case is presented in which a guidewire, during subclavian catheterization in a 63 years old patient, became knotted outside the vein, behind the clavear head of the sternocleidomastoid muscle. The wire was easily removed by surgical approach and the post operative course was uneventful. The causes of this complication are discussed and a few main points are emphasized when the Seldinger technique is employed for subclavian vein catheterization.

Direct enantiomeric separation of flavanones by high performance liquid chromatography using various chiral stationary phases.

The performance of four chiral liquid chromatographic columns (Chiralcel OA, OJ, OC, OD) was studied with respect to the enantioseparation of flavanones and some derivatives. The effect of mobile phase composition on the retention time and stereo-selectivity was studied. A good enantioseparation (alpha up to 1.45) was achieved for most of the racemates. Further, the elution order of the enantiomers from the chiral stationary phases has been determined by using a circular dichroism based detection system.

[Kawasaki syndrome: review of the literature and presentation of 4 clinical cases]. / La sindrome di Kawasaki: revisione della letteratura e presentazione di quattro casi clinici.

Four new cases of Kawasaki Syndrome are presented. The Authors discuss the etiopathogenetic hypothesis, point out the usefulness of treatment with ASA + high dose intravenous gammaglobulins, underline the risk of cardiac complication.

Influence of oral contraceptives on fasting gallbladder volume.

A total of 615 healthy fertile women (518 pill users and 97 non-users) were examined by real-time ultrasonography for fasting gallbladder volume, gallstones and biliary dysmorphism. None of the six examined combinations of oral contraceptives appeared to influence fasting gallbladder volume significantly. When fasting gallbladder volumes were reanalyzed according to the presence or absence of recognized biliary risk factors, significant modifications were detected, in both pill users and non-users. These changes related only to age and parity. Relative risks of cholelithiasis and biliary dysmorphism were not affected by contraceptive treatment.

PIP: In Italy, researchers used real-time ultrasonography for fasting (no solid food for 24 hours) gallbladder volume to compare data on 518 women using low-dose, combined oral contraceptives (OCs) for 12-120 months with data on 97 women who had never used OCs to examine the effect of OCs on the gallbladder. The 615 healthy, fertile 16-52 year old women were clients of Contraceptive Counseling Services of the Department of Obstetrics and Gynaecology at the University of Ferrara and the Local Sanitary Unit. No significant difference in fasting gallbladder volumes existed between cases and controls. OC use was not associated with fasting gallbladder volume in relation to duration of treatment, family cholelithiasis, smoking, or age. As parity increased so did fasting gallbladder volume in both groups (p = 0.04 for controls and p = 0.01 for cases). Fasting gallbladder volume increased with age in both groups but not significantly so. Biliary dysmorphism existed in 17.8% of OC users and 24.7% of controls. Cholelithiasis was present in 2.9% of OC users and 3.1% of controls. OC use did not affect the relative risk of biliary dysmorphism and cholelithiasis (0.66 and 0.95, respectively). In conclusion, low-dose OCs do not affect gallbladder motility.