Finding the best therapeutic approach for PCOS: the importance of inositol(s) bioavailability.

Broadening clinical evidence has markedly designated inositol(s) as a common and effective therapeutic approach for PCOS and infertility. Although considerable research has been focused on the use in clinical practice of myo-inositol (myo-ins) and D-chiro-inositol (D-chiro-ins), the two major inositol stereoisomers, less attention has been paid to their bioavailability. Therefore, the aim of this paper is to gather and analyze information on inositol(s) bioavailability, to better delineate its optimal concentration for scientific and clinical purposes. Throughout the search in PubMed, Google Scholar, and ResearchGate we identified only two studies that investigated the pharmacokinetic (PK) profile of different myo-ins administrations. This analysis found no advantage in terms of PK for single 4 g dosing of myo-ins compared to 2 g twice a day, which allowed to get a 24-hour coverage, contrary to the singular dose. Indeed, the differences regarding the area under the curve (AUC) between the two PK profiles are linked only to the maximum concentration (Cmax) but not to the time variable. In conclusion, splitting the therapeutic dosage of 4 g myo-ins in two distinct administrations seems to be the best approach for a full-day coverage.

N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review.

OBJECTIVE: Biofilms are microbial communities consisting of bacteria, extremely capable to self-reproduce on biological surfaces, causing infections. Frequently, these biofilms are resistant to classical antibacterial treatments and host immune response. Thus, new adjuvant molecules are mandatory in clinical practice. N-acetylcysteine (NAC), a precursor to the antioxidant glutathione, has been investigated for its effectiveness both in inhibiting biofilm formation and in destroying developed biofilms. The aim of our study was to conduct a systematic literature review of clinical trials involving NAC as adjuvant treatment to eradicate pre-formed mature biofilms and to inhibit new biofilm production. MATERIALS AND METHODS: A careful analysis of the Medline was conducted and eight studies were selected according to the following criteria: site of infection, kind of bacteria, design of the research, dose of the treatment, administration, biological effects and results. We fixed an arbitrary scale of scores from 0 (lowest score) to 5 (highest score) for each criterion and a threshold value of 3. RESULTS: The studies analyzed, with score over 3, suggested a potential role for NAC as adjuvant molecule in the treatment of bacterial biofilms, with an excellent safety and efficacy profile. NAC, in combination with different antibiotics, significantly promoted their permeability to the deepest layers of the biofilm, overcoming the problem of the resistance to the classic antibacterial therapeutic approach. CONCLUSIONS: Overall, these results are encouraging to a more widespread clinical use of NAC, as adjuvant therapy for microbial infections followed by biofilm settle, which may occur in several body districts, such as the vaginal cavity.

Inositol: history of an effective therapy for Polycystic Ovary Syndrome.

Inositol is a physiological compound belonging to the sugar family. The two inositol stereoisomers, myo-inositol and D-chiroinositol are the two main stereisomers present in our body. Myo-inositol is the precursor of inositol triphosphate, a second messenger regulating many hormones such as TSH, FSH and insulin. D-chiroinositol is synthetized by an insulin dependent epimerase that converts myo-inositol into D-chiro-inositol. Polycistic Ovary Syndrome (PCOS) is a metabolic and hormonal disorder and a common cause of infertility. Insulin resistance and the consequent hyperinsulinaemia contribute to hyperandrogenism development, typical marker of PCOS. In these patients myo and/or D-chiro-inositol administration improves insulin sensivity while only myo-inositol is a quality marker for oocytes evaluation. Myo-inositol produces second messengers for FSH and glucose uptake, while D-chiroinositol provides second messengers promoting glucose uptake and glycogen synthesis. The physiological ratio of these two isomers is 40:1 (MI/DCI) and seems to be an optimal approach for the treatment of PCOS disorders.

Oral contraceptives and changes in nutritional requirements.

Oral contraceptives (OCs) are a major class of prescription drug, used by a large proportion of women starting from early adolescence. Much research has been conducted to investigate the physiological changes that occur in women who take OCs. These include changes in general health as well as in nutritional needs. In terms of nutrition, several studies investigated whether women on OCs need different amounts of some vitamins and minerals. In particular, a report from the World Health Organization (WHO) points out that the influence of OCs on nutrient requirements is a topic of high clinical relevance and should, therefore, receive great attention. It has been shown that the key nutrient depletions concern folic acid, vitamins B2, B6, B12, vitamin C and E and the minerals magnesium, selenium and zinc. Most research has focused on the levels of these vitamins and minerals in the blood of women who take OCs compared to women who do not. Since women who take OCs not always have adequate diet, may have unhealthy life style or may suffer from pathologies of malabsorption, the possibility to prevent vitamin and mineral deficiencies by taking appropriate dietary supplements should be considered a first-line approach by clinicians.

Comparison between tungsten and steel polypectomy snares: evaluation of depth of colonic thermal wall injury in a pig model.

BACKGROUND AND STUDY AIMS: Thermal injury of the colonic wall during polypectomy may induce complications such as bleeding and perforation. To date, the role of the snare material in these injuries has not been examined. The aim of this study was to evaluate the depth of colonic post-polypectomy thermal wall injury induced by tungsten and steel endoscopic snares, in an effort to reduce electrosurgery-related complications. MATERIALS AND METHODS: This was a single tertiary center experimental study in a porcine model. A total of 90 polypectomies where performed in three live pigs under general anesthesia, using both steel and tungsten snares by cut, coagulation, and blend current modes. The pigs were then euthanized and their colons examined histologically. RESULTS: Steel snares induced significantly deeper tissue injury than tungsten snares in the pure cut mode (Pearson χ2 = 6.136, P = 0.013). The ordinal logistic regression analysis showed that the current mode and snare material were significantly associated with the ordinal score for the depth of injury. Thus, cut mode was positively associated with a lower score and coagulation mode with a higher score. In addition, tungsten was significantly associated with a lower depth of tissue injury. CONCLUSIONS: Due to its inherent electrical properties, tungsten is very well suited for manufacture into electrosurgical endoscopic devices. Thus, tungsten snares may be advantageous for routine use in endoscopic polypectomy, although further studies are needed to confirm these promising findings in human patients.

Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials.

Polycystic ovary syndrome (PCOS) affects 5%-10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity. Several studies have reported that insulin resistance is common in PCOS women, regardless of the body mass index. The importance of insulin resistance in PCOS is also suggested by the fact that insulin-sensitizing compounds have been proposed as putative treatments to solve the hyperinsulinemia-induced dysfunction of ovarian response to endogenous gonadotropins. Rescuing the ovarian response to endogenous gonadotropins reduces hyperandrogenemia and re-establishes menstrual cyclicity and ovulation, increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo-inosiol (MYO). Previous studies have demonstrated that MYO is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. With the present review, we aim to provide an overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS.

Contribution of myo-inositol and melatonin to human reproduction.

Diet is a critical factor for the development of both embryo and fetus, as well as maternal health. In particular, two natural molecules have been shown to exert beneficial effects on fertility, pregnancy wellness and embryo development: myo-inositol and melatonin, whose requirements increase during pregnancy. In the present review, we summarize the most important functions of melatonin and myo-inositol on male and female reproductive systems (oocyte quality and development, sperm quality), on the maintenance of a physiological pregnancy and on embryo development.

Inositol safety: clinical evidences.

Myo-inositol is a six carbon cyclitol that contains five equatorial and one axial hydroxyl groups. Myo-inositol has been classified as an insulin sensitizing agent and it is commonly used in the treatment of the Polycystic Ovary Syndrome (PCOS). However, despite its wide clinical use, there is still scarce information on the myo-inositol safety and/or side effects. The aim of the present review was to summarize and discuss available data on the myo-inositol safety both in non-clinical and clinical settings. The main outcome was that only the highest dose of myo-inositol (12 g/day) induced mild gastrointestinal side effects such as nausea, flatus and diarrhea. The severity of side effects did not increase with the dosage.

Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common cause of infertility due to menstrual dysfunction, and the most promising treatments for this disease are insulin sensitising agents. Myo-inositol and D-chiro-inositol are insulin sensitizing agents used in PCOS treatment. In the present paper, we aimed to compare the effects myo-inositol and D-chiro-inositol on oocyte quality in euglycemic PCOS patients. MATERIALS AND METHODS: Eighty-four euglycemic PCOS patients, undergoing ovulation induction for ICSI, were recruited for this study. Forty-three participants received MyoInositol 2 g twice a day and forty-one patients received D-chiro inositol 0.6 g twice a day. RESULTS: The results of our study showed that the total number of oocytes retrieved did not differ in the two treatments groups. However, the number of mature oocytes was significantly increased in the myo-inositol group compared to D-chiro-inositol. Concurrently, the number of immature oocytes decreased in myo-inositol treated patients. Furthermore, the myo-inositol-treated group showed an increase in the mean number of top quality embryos and in the total number of pregnancies compared to the D-chiro-inositol-treated group. CONCLUSIONS: Our data show that, in PCOS patients having a normal insulin response, myo-inositol treatment rather than D-chiro-inositol is able to improve oocyte and embryo quality during ovarian stimulation protocols.

Endometrial carcinoma clinical management: results of a regional survey.

In Southern regions of Italy, many women affected by oncologic pathology go to larger towns to referral hospitals to be treated. However there is the impression that this does not apply to endometrial cancer, which affects older women less prone to seek care far from home. To verify this premise and to ascertain the quality of treatment these patients received, and the degree of compliance of their treatment with the International Federation of Gynecology and Obstetrics (FIGO) recommendations, a database was created collecting information concerning the clinical management of endometrial cancer in 13 different gynecological units in the Campania region. We confirmed that endometrial carcinoma, the most frequent oncologic pathology in all participating units, was treated independently from the dimensions of all of these units. The adopted diagnostic and therapeutic procedures seemed to be largely compliant with FIGO guidelines. Limited dishomogeneity only regarded the smallest units. Overall, a good quality of treatment seemed to be given to women affected by this pathology who wanted to be treated in, or close to, their town of residence.

Report of two cases of controlateral groin recurrence after ipsilateral groin node dissection for vulval cancer.

Among the more conservative management strategies intended to individualize the surgical treatment of vulval cancer, ispilateral groin dissection is proposed for T1-T2 lateral lesions. Since patients found negative for metastatic nodes in the ipsilateral groin and developing unexpected recurrences in the controlateral non-dissected groin have a poor outcome, it is useful to report such cases to better evaluate the safety of these less aggressive surgical procedures.

[Carcinosarcoma of the gallbladder]. / Il carcinosarcoma della colecisti.

The authors analyse and comment on a case of carcinosarcoma of the gallbladder which they have recently observed. Given the rarity of this form of cancer, it is interesting to note that this case presents some peculiar aspects which have not been recorded in the few cases previously published on the subject. The peculiarities are such that they require a revision of what have until now been considered as intrinsic characteristics in the clinical observation of this kind of cancer. The authors maintain that the peculiarities of this case concern: a) the clinic onset of the illness and the relative aspecific symptomatology: b) that fact that laboratory tests did not signal any biochemical alteration; c) that the instrumental investigation's results pointed toward a non neoplastic pathology; d) that even the intra-operatory examination did not reveal any suspicious element; and last but by no means least the good survival of the patient which is definitely superior to other cases already reported in literature. The neoplasia, which manifested itself through a hemorrhage in the gallbladder, represented in fact the very initial stage of the illness, a condition rarely observed.

Efficacy and tolerability of brodimoprim at two different dosage schedules in the treatment of acute uncomplicated bacterial cystitis: comparative study vs. pefloxacin.

In an open study, 172 male and female adult patients with acute uncomplicated bacterial cystitis were randomly allocated to three treatment groups. Two groups received brodimoprim 200 mg tablets as follows: a single dose of two 200 mg tablets on day 1, followed by one tablet per day on days 2 and 3 (58 patients); or a single daily dose of two tablets, for 2 days (63 patients). The third group received a single dose of pefloxacin, as two 400 mg tablets, for 1 day (51 patients). Complete urinalysis, sediment and urine culture examinations were carried out before treatment and 10 days after the last dose. Evaluation also comprised, at the time of enrolment and 48 h after the last dose, measurement of corporal temperature and assessment of symptoms (dysuria, pollakiuria, strangury, suprapubic pain, burning sensation during urination and urgency) on a 4-point scale. The eradication rate for the pathogen concerned was 98.3% and 96.7% in the groups receiving brodimoprim for 3 and 2 days, respectively, and 92.8% in the pefloxacin group (between-group comparison n.s.). There was significant regression of symptoms (P < 0.001) in the three groups (between-groups comparison n.s.). Mainly gastrointestinal adverse events occurred in 3 patients receiving brodimoprim for 2 days and in 4 patients from each of the other two groups.

Postmaturity: how far is it a clinical entity in its own right?

In 1990 we adopted a protocol of antepartum testing for all booked pregnant patients, permitting healthy pregnancies to go beyond 42 completed weeks of gestation. This retrospective study regards 84 patients delivering after 42 completed weeks of pregnancy and a control group of 1351 patients delivering after 37 completed and before 41 completed weeks of pregnancy. Records were revised for maternal age and parity, previous obstetric history, managing and complications of the actual pregnancy, labour and mode of delivery, neonatal biometric data and outcome. Only 4 patients delivered after 43 completed weeks of gestation, while none in the series delivered later than 44 completed weeks after the beginning of the last menstrual period. The overall frequency of caesarean birth was higher, but not significantly, in study group. Average neonatal birthweight and length were significantly greater in the study group. No significant difference in neonatal outcome was observed between study and control groups in terms of perinatal mortality. Low 1' Apgar score was significantly more frequent in the study group, but a similar frequency of 5' Apgar score and need for intensive care was observed in the two groups.

[Perforation of the sigmoid caused by ingestion of foreign body]. / Perforazione del sigma da ingestione di corpo estraneo.

Dating from October 1987 to January 1995 we have observed 24 patients who swallowed an extraneous object. Tree of them underwent a surgical operation whereas the remaining 21 were monitored endoscopically. Our team use to operate when the extraneous object, for its shape or dimension, comes to a stop along the intestine, causing a potential of existent complication. In 2 of the 3 cases above mentioned, the diagnosis came out from a abdomen x-ray which put into evidence a clothes peg stopped at level with the first jejunal ansa and an open pin which had performed an ileal ansa. As far as concerns the third case, we were compelled to operate without a preoperative diagnosis as the patient, mentally disabled, swallowed a sharpened, not x-rayed extraneous object (a toothpick). When swallowed, a toothpick usually causes lesions in the higher stretch of the digestive system. It is very difficult to spot the toothpick position for it slack x-opacity, even when the lesion caused by it is clearly visible. The sigma perforation, caused by the swallow of an object, rarely happens. Authors have reported a case to be pointed out for its pathogenetic originality.

[Bleeding gastric leiomyoma: diagnostic error solving an emergency case]. / Leiomioma gastrico sanguinante: errore di indagine diagnostica risolutore di un caso chirurgico d'urgenza.

Although rare, benign gastric tumours are frequently encountered in the recent years thanks to the greater accuracy of diagnostic investigations. The Authors report their experience in a case of bleeding gastric leiomyoma which caused preoperative diagnostic problems due to the extraluminal development of the tumor and to diagnostic investigation errors. An easy diagnosis of this type of tumor is not therefore a rule, but, as in the case reported, may be rather insidious especially in small leiomyomas with an extra or intraparietal development and aspecific symptomatology masquereding other more frequent pathologies.

[Conservative treatment of tubal pregnancy with parenteral administration of methotrexate. Case contribution]. / Il trattamento conservativo della gravidanza tubarica mediante somministrazione parenterale di metotressato. Contributo casistico.

Three subjects with tubal ectopic pregnancy were treated with intravenous administration of methotrexate followed by oral administration of folinic acid. The treatment was effective in obtaining the resolution of ectopic pregnancies in all cases. Tubal patency was also preserved.