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.

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.

[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.

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.

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.

[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.

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.

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.

[Expert systems in medical emergencies]. / I sistemi esperti nell'emergenza medica.

Computers have already been introduced into the field of medical applications and many support systems have been developed. Recently expert or knowledge-based systems have been employed in some specific fields. A project for the creation of an expert system for use in toxicological emergencies is presented. This system is designed to give the physician continuous support and to employ computer formulae as similar as possible to medical reasoning. For this reason, medical knowledge was examined and the event graphs, frames and production rules to represent it were chosen.

[Changes of plasmatic amino acids in various cases of acute hepatic necrosis and insufficiency in man]. / Variazioni degli aminoacidi plasmatici in alcuni casi di necrosi ed insufficienza epatica acuta nell'uomo.

Changes in total and individual plasma amino acid were examined in subjects with necrosis of the liver and acute insufficiency. Quantitative variations in single amino acids and their percentages were noted in all cases. The extent of such change and the number of amino acids involved were roughly proportional to the degree of insufficiency. A continuous and persistent increase in total blood amino acids can be regarded as a poor prognostic sign, especially if accompanied by a sharp fall in necrosis enzymes. Such an increase, in fact, was only observed in extremely serious cases.

[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.

[Mebendazole in the therapy of hydatidosis]. / Il mebendazolo nella terapia dell'idatidosi.

The effectiveness of mebendazole as adjuvant treatment in hydatidosis was evaluated in 19 patients; 12 were treated both before and after surgery, 6 were not treated, one had primary treatment only, owing to the refuse of surgery. Mebendazole was administrated at the dosage of 30-50 mg/kg/day po for 30 days followed by a washout of 15 days, for a mean of 4 cycles (range 1-7) and 12 cycles (range 1-24) before and after surgery, respectively. Patients were monitored by total IgE, specific anti-echinococcus IgE and IgG, at diagnosis, just before surgery and thereafter every six months. Antibody titer decrease was observed soon after the first cycles of medical treatment before surgery, as well as a clear-cut drop after surgery, followed by a continuing decrease after the following cycles of mebendazole. Relapse of disease was observed in two patients only at one and two years after surgery respectively. These preliminary results seem to point out that mebendazole might play a role in the treatment of hydatidosis as adjuvant of surgical therapy.

[Therapy with L-thyroxine in thyroid struma. Study with ultrasonic evaluation]. / La terapia con L-tiroxina nello struma tiroideo. Studio con valutazione ecotomografica.

L-thyroxine therapy in thyroid goiter. Study with ultrasound imaging evaluation. The literature contains conflicting reports regarding the treatment of thyroid goiter. We evaluated the efficacy of thyrotropin-suppressive therapy with L-thyroxine to reduce the goiter. We studied two groups of 15 and 19 patients with euthyroid goiter for a period of six months: the former were untreated, the latter received L-thyroxine. Six patients represented the controls. All patients treated had suppressed thyrotropin secretion (as evaluated by immunoradiometric assay); sonography was used to measure the goiter. We found no statistically significant difference in size nodule between the two groups. Therapy was also unable to prevent the formation of new nodules.

[The "diagnostic day hospital." A proposal for functional support by hospital services and primary care]. / Il day hospital diagnostico. Una proposta di supporto funzionale dei servizi ospedalieri e di assistenza di base.

The general lack of nurses and the attention due to the purposes of efficiency, effectiveness and economy of hospital services oblige to better the cooperation between attending and family physicians, to improve the resources, the productiveness of clinicopathology, the use of daily hospital services (such as ambulatories, daily hospitalization and treatments) and emergencies. For this end the authors propose the realization of a day hospital which mainly aim is the diagnostic (D.H.D.) of internal medicine. The admission will be acted by a doctor of the emergency department and of the reception. The day hospital will be functionally linked up with the services of emergency dpt. and reception and with the outpatients' department. Therefore useful both for the attending and family physicians. This kind of day hospital shouldn't substitute the specialities (such as hematology, oncology, psychiatry, dialysis, rehabilitation, etc.) which finalities are principally the therapy and check-up of known patients who follow a treatment by a specialistic department. The D.H.D. should grant the following functions: --Diagnosis or provable orientation in case the doctor of the emergency dpt. or the specialist in ambulatory shouldn't be able to perform them immediately; --Clinical control of cases coming from the emergency dpt.; --Planning of therapeutic program and carrying out of ambulatory therapies that cannot be deferred, of cases coming from the emergency dpt. or reception. Then, is attributable to the D.H.D. the hospital statistics that: --requires clinical observation that cannot be deferred; --requires unerring, prompt and complex diagnostic orientation in order to decide the kind of ward where the hospitalization should be done; --if needed, hospital therapeutic intervention that cannot be deferred, incompatible with the operative possibilities of the D.H.D. The authors also deal with operative relations between D.H.D. and other hospital services, the staff organization, the location, dimension and functional attribution of the head office, the purchases and availability of sanitary fittings and furnishings. Finally, the authors estimate the effectiveness of D.H.D. as far as the reduction of continuative hospitalization is concerned.

[Finnish-type nephrotic syndrome: report of the fourth case in Italy and review of the literature]. / Sindrome nefrosica di tipo finlandese: segnalazione del quarto caso in Italia e revisione della letteratura.

The Authors have studied anamnestic, clinical and morphological data of a case of Congenital Nephrotic Syndrome of Finnish type (CNS-FT). Similarly to the first case reported in Italy, the patient was born by consanguineous parents. For the determination of the real incidence of this disease, in countries shere CNS-FT is rarely signalled, the importance of histopathological examination of the kidney is emphasized.

[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.

[The echocardiographic evaluation of multiply transfused thalassemia patients over the age of 10]. / Valutazione ecocardiografica in talassemici politrasfusi con età superiore a 10 anni.

Today cardiomyopathy is the main cause of death of patients with thalassemia disease since the second decade of their lives. Echocardiography is a useful means to put into evidence cardiac alterations before the appearance of the clinical marks of cardiac failure.

[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.

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.