Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes.

The present manuscript stems from evidence, which indicates that specific wavelength produce an activation of the autophagy pathway in the retina. These effects were recently reported to synergize with the autophagy-inducing properties of specific phytochemicals. The combined administration of photo-modulation and phytochemicals was recently shown to have a strong potential in eliciting the recovery in the course of retinal degeneration and it was suggested as a non-invasive approach named "Lugano protocol" to treat age-related macular degeneration (AMD). Recent translational findings indicate that the protective role of autophagy may extend also to acute neuronal injuries including traumatic neuronal damage. At the same time, very recent investigations indicate that autophagy activation and retinal anatomical recovery may benefit from sound exposure. Therefore, in the present study, the anatomical rescue of a traumatic neuronal loss at macular level was investigated in a patient with idiopathic macular hole by using a combined approach of physical and chemical non-invasive treatments. In detail, light exposure was administered in combination with sound pulses to the affected retina. This treatment was supplemented by phytochemicals known to act as autophagy inducers, which were administered orally for 6 months. This combined administration of light and sound with nutraceuticals reported here as Advanced Lugano's Protocol (ALP) produced a remarkable effect in the anatomical architecture of the retina affected by the macular hole. The anatomical recovery was almost complete at roughly one year after diagnosis and beginning of treatment. The structural healing of the macular hole was concomitant with a strong improvement of visual acuity and the disappearance of metamorphopsia. The present findings are discussed in the light of a synergism shown at neuronal level between light and sound in the presence of phytochemicals to stimulate autophagy and promote proliferation and neuronal differentiation of retinal stem cells.

Noradrenergic substrates sensing light within brainstem reticular formation as targets for light-induced behavioral and cardiovascular plasticity.

The occurrence of pure light exerts a variety of effects in the human body, which span from behavioral alterations, such as light-driven automatic motor activity, cognition and mood to more archaic vegetative functions, which encompass most organs of the body with remarkable effects on the cardiovascular system. Although empirical evidence clearly indicates occurrence of these widespread effects, the anatomical correlates and long-lasting changes within putatively specific neuronal circuitries remain largely unexplored. A specific role is supposed to take place for catecholamine containing neurons in the core of the brainstem reticular formation, which produces a widespread release of noradrenaline in the forebrain while controlling the vegetative nervous system. An indirect as well as a direct (mono-synaptic) retino-brainstem pathway is hypothesized to rise from a subtype of intrinsically photosensitive retinal ganglion cells (iPRGCs), subtype M1, which do stain for Brn3b, and project to the pre-tectal region (including the olivary pre-tectal nucleus). This pathway provides profuse axon collaterals, which spread to the periacqueductal gray and dorsal raphe nuclei. According to this evidence, a retino-reticular monosynaptic system occurs, which powerfully modulate the noradrenergic hub of reticular nuclei in the lateral column of the brainstem reticular formation. These nuclei, which are evidenced in the present study, provide the anatomical basis to induce behavioral and cardiovascular modulation. The occurrence of a highly interconnected network within these nuclei is responsible for light driven plastic effects, which may alter persistently behavior and vegetative functions as the consequence of long-lasting alterations in the environmental light stimulation of the retina. These changes, which occur within the core of an archaic circuitry such as the noradrenaline-containing neurons of the reticular formation, recapitulate, within the CNS, ancestral effects of light-driven changes, which can be detected already within the retina itself at the level of multipotent photic cells.

Pregnancy and Infants' Outcome: Nutritional and Metabolic Implications.

Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.

Risk factors for Early Childhood Caries in Italian preschoolers: A cross-sectional analysis.

AIM: Early childhood caries (ECC) represent a relevant public health issue in paediatric population globally. The current study aimed to investigate the main risk factors of this condition. METHODS: This is a cross-sectional study carried out at the Child Dentistry Clinics of the Istituto Stomatologico Italiano, Milan, Italy, including patients aged 12-71 months and their parents. Demographical data, anthropometric measurements, oral hygiene and health assessment, and children's eating habits were collected. CONCLUSION: Our findings, according to recommendations, suggest that the prevention of ECC needs to begin in infancy. Oral health providers, physicians, nurses, and other health care personnel play an important role in educating parents about their child's oral and dental care and food choices.

Integrative multidisciplinary approaches by the Integrative Medicine Research Group (IMRG): a new frontier in cancer setting.

This conference addresses the topic of integrative, multidisciplinary approaches to cancer settings according to evidence-based medicine. The multidisciplinary approach of the researchers involved characterizes this new and complex scenario. The Integrative Medicine Research Group (IMRG) has always been committed to the activities and dissemination of CAM in cancer patients, focusing on the safety and efficacy of these approaches. Thus, one of the main goals of IMRG is to demonstrate that CAM can support cancer patients during treatment and improve their quality of life and survival. In addition, IMRG's multidisciplinary network is ever vigilant in assessing the risks of interactions between cancer drugs and nutraceuticals. We hope that the integrative medicine approach can be transferred to the level of all chronic diseases, including oncology.

Influence of the type of breastfeeding as a risk or protective factor for the onset of malocclusions: a systematic review.

AIM: The correlation between malocclusions in deciduous dentition and type of breastfeeding has been described by many authors in numerous articles. The aim of this article is to investigate the literature about this important topic. MATERIALS: The research was conducted by querying the following databases: PubMed, EBMR, Cochrane Library, Web of Sciences, Medline, Web of Sciences, Ovid and Embase. The key words were: "infant" OR "baby", AND "breastfeeding" AND "malocclusion". As with similar literature review papers, the PRISMA-P (Preferred Reporting Items for Systematic Reviews Protocols) was used. The examined articles were of the following types: randomised controlled trials (RCTs), case-control studies and cohort studies. For the qualitative analysis of the selected studies, it was employed the NOS scale (Newcastle-Ottawa Quality Assessment Scale). CONCLUSION: Two hundred and fifty articles were selected. After filtering out the articles deemed irrelevant or with obvious bias, only 16 articles were left. From our results, it can be concluded that breastfeeding seems to play a decisive role in preventing the onset of posterior cross-bites and Class II malocclusions, and that this protective effect appears to be time-dependent.

Influence of caffeine and midazolam on gamma-aminobutyric acid-evoked responses in the frog spinal cord.

The recently reported potentiation of gamma-aminobutyric acid (GABA) evoked depolarizations by caffeine in the frog spinal cord might involve an interaction with GABA-linked benzodiazepine receptors. This possibility was investigated using a new potent benzodiazepine, midazolam, and a benzodiazepine antagonist, Ro 147437. Caffeine or midazolam enhanced the amplitude of submaximal GABA responses by about 50%; when equieffective enhancing doses of these compounds were simultaneously applied, GABA depolarizations were usually depressed below control levels. It was however possible to detect a narrow range of concentrations of midazolam which had an additive effect to the enhancement by caffeine. Ro 147437 did not block caffeine-induced potentiations of GABA responses. It is suggested that caffeine and benzodiazepines have distinct modes of action in modulating GABA-induced depolarizations in the in vitro spinal cord of the frog.

Two-dimensional contrast echocardiography with carbon dioxide in the detection of congenital cardiac shunts.

Medically pure (100%) carbon dioxide directly injected into a peripheral vein was used for 2-dimensional contrast echocardiography in 134 patients with an arteriovenous shunt demonstrated by cardiac catheterization and cineangiography, Qp/Qs ratios of 1.5 to 3.7, pulmonary-to-systemic peak systolic pressure ratios of 0.2 to 0.8 and no oximetrically demonstrable venoarterial shunt. Two patients with transposition of the great arteries, intact ventricular septum and a Senning operation as well as 30 normal subjects of comparable age also were studied. In patients with an atrial septal defect, the gas microbubbles opacified the left atrium. In patients with a ventricular septal defect, the gas microbubbles opacified the left ventricle, whereas the left atrium was free of contrast. In all patients with patent ductus arteriosus, the gas microbubbles opacified the abdominal aorta, whereas the left atrium, left ventricle, aortic root and aortic arch remained free of contrast. In 2 patients in whom an aneurysm of the sinus of Valsalva ruptured into the right ventricle, the "negative" contrast effect permitted localization of the shunt. In 2 patients with transposition of the great arteries, an intact ventricular septum and a Senning operation, the intracardiac flow pattern was clearly demonstrated. No complication was observed. We conclude that pure carbon dioxide directly injected into a peripheral vein is a safe and advantageous echocardiographic contrast material. Because of its greater diffusibility in comparison with oxygen and fluid contrast media, small venoarterial shunting can be detected in defects such as atrial septal defect, ventricular septal defect and patent ductus arteriosus, in which only an arteriovenous shunt can be demonstrated by oximetry.

Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.

We examined 5HT1a-mediated ACTH release in patients with chronic fatigue syndrome (CFS) using a between-subjects design. Patients attending a specialist outpatient clinic for CFS, who fulfilled CDC criteria, together with age- and sex-matched healthy comparison subjects, were recruited. Subjects had a cannula inserted in a forearm vein at 0830 h and were allowed to relax until 0900 h, when baseline bloods for ACTH and cortisol were drawn. They were then given ipsapirone 20 mg PO and further blood for hormone estimation was taken at +30, +60, +90, +120 and +180 min. Baseline ACTH and cortisol levels did not differ between the two groups. Release of ACTH (but not cortisol) in response to ipsapirone challenge was significantly blunted in patients with CFS. We conclude that serotonergic activation of the hypothalamic-pituitary-adrenal axis is defective in CFS. This defect may be of pathophysiological significance.

Caffeine-induced potentiation of GABA effects on frog spinal cord: an electrophysiological study.

A parasagittal slice of the frog spinal cord was kept in vitro for electrophysiological recordings from dorsal and ventral roots. Low concentrations of caffeine (50 microM) which had relatively small effects on baseline electrical activity, increased the depolarizing action of GABA on dorsal root fibres by 50%. A similar result was also obtained when GABA motoneuronal responses were tested. On dorsal roots the potentiation of GABA responses by caffeine was reflected by a significant decrease in GABA ED50 value without change in the maximal response amplitude; this enhancing action of caffeine was not blocked by bicuculline (5 microM) but was abolished by flurazepam (5 microM) or by Ca2+ antagonists (Mn2+ and Cd2+). Blockade of interneuronal activity by procaine left the potentiating action of caffeine unchanged. High doses of caffeine (up to 1 mM) produced a seemingly non-competitive antagonism of GABA responses. We suggest that caffeine can modulate GABA responses through two different mechanisms: a potentiation of GABA effects (seen with low doses of caffeine) probably due to Ca2+ mobilization and an antagonism of GABA responses (typically seen with large doses of caffeine) perhaps caused by block of GABA receptor-activated channels. This novel caffeine-GABA interaction may be useful to interpret some of the effects of caffeine on mammalian behaviour.

GABA-induced depolarizing responses of the frog spinal cord can be either enhanced or antagonized by the benzodiazepine midazolam and the methylxanthine caffeine.

The isolated frog spinal cord was used as a test system to investigate the interactions of midazolam and caffeine with GABA-evoked responses recorded from dorsal afferent fibres. Midazolam was a potent stimulator (ED50 = 1 nM) of GABA effectiveness on this preparation since the ED50 value for GABA was nearly halved. The enhancing action of midazolam was apparently produced via activation of benzodiazepine receptor mechanisms with no detectable receptor cooperativity and with a rather high sensitivity to the selective benzodiazepine antagonist Ro 14-7437 (antagonist ED50 = 2.5 nM). Responses to glutamate, glycine or high K+ were unchanged in midazolam solutions. When midazolam was applied in concentrations equal or larger than 100 nM, antagonism of GABA responses was evident. Caffeine (50 microM) also potentiated GABA responses through a mechanism distinct from benzodiazepine receptor activation as this action of caffeine was insensitive to Ro 14-7437. Mixtures of low doses of caffeine and midazolam frequently antagonized GABA responses. It is suggested that the blockade of GABA responses by caffeine-midazolam mixtures might account for the reversal of some behavioural actions of these substances even if they probably operate through separate pharmacological mechanisms.

Potentiating action of midazolam on GABA-mediated responses and its antagonism by Ro 14-7437 in the frog spinal cord.

The effect of midazolam, a new water-soluble benzodiazepine, on an in vitro slice preparation of the frog spinal cord was investigated using electrophysiological recordings. Midazolam potently (ED50 = 1 nM) enhanced the depolarizing action of GABA on primary afferent fibres while leaving the depolarizing effect of glutamate, glycine or high K+ solutions unchanged. Concentrations of midazolam higher than 100 nM had an antagonistic effect on GABA responses. Ro 14-7437 was a powerful and selective antagonist of the midazolam potentiation without affecting control responses to GABA, glutamate or high K+. The antagonism of GABA responses induced by high doses of midazolam was not sensitive to Ro 14-7437. Our data suggest that midazolam is a very potent and selective modulator of GABA responses: this finding illustrates that electrophysiological techniques can detect specific effects of very low concentrations of benzodiazepines on a CNS slice preparation with well preserved architectural organization.

The effect of D-alpha-aminoadipate on excitatory amino acid responses recorded intracellularly from motoneurones of the frog spinal cord.

The excitatory responses to amino acids were recorded intracellularly from motoneurones in the isolated frog spinal cord and the effect of the antagonist D-alpha-aminoadipate examined. An unusual profile of antagonism was obtained in that with 50-100 microM D-alpha-aminoadipate the depolarization to quisqualate was unaffected (or slightly potentiated) while those to L-glutamate, L-aspartate and N-methyl-D-aspartate were all considerably attenuated. D-alpha-aminoadipate did not influence passive membrane properties although a small hyperpolarization was sometimes evident. Dorsal root evoked excitations of motoneurones, particularly those using low strength stimulation, were also susceptible to antagonism by D-alpha-aminoadipate. These data suggest a separate neuroeffector/receptor mechanism for quisqualate compared to L-glutamate, L-aspartate and N-methyl-D-aspartate.

Antinociceptive properties of the methanolic extract obtained from Ipomoea pes-caprae (L.) R. Br.

Ipomoea pes-caprae is a medicinal plant used in many countries for the treatment of several ailments, including inflammatory and algesic processes. The present study describes the antinociceptive effects of the methanolic extract and two fractions obtained from aerial parts of this plant. The results indicated that both methanolic extract and two fractions (ethyl acetate and aqueous) exhibited considerable antinociceptive activity against two classical models of pain in mice. Methanolic extract presented a calculated ID50 value of 33.8 mg/kg, i.p. against writhing test and also inhibited both phases of pain (neurogenic and inflammatory) of the formalin test with ID50 of 37.7 and 12.5 mg/kg, i.p. for the first and second phase, respectively. Preliminary phytochemical analysis suggested the presence of steroids, terpenoids, alkaloids and flavonoids. These findings support, at least in part, the popular use of I. pes-caprae to treat dolorous processes.

[Apical pulmonary fibrosis in the course of ankylosing spondyloarthritis]. / Fibrosi polmonare apicale in corso di spondiloartrite anchilosante.

Two cases of an association between lung TB and ankylosing spondyloarthritis are presented. In the first case, spondyloarthritis appeared about 1 yr after fibrocavitary lesions of the LSD. The literature contains only 1 similar case, in which the gap was two years. In the second case, such lesions appeared 8 yr after spondyloarthritis. Neither patient received radiation treatment. The first received cortisone for massive joint inflammation when typical lung TB lesions were already evident. It is felt that these two additions to the literature are of interest in clarifying the delicate questions of diagnosis that arise when ankylosing spondylarthritis is accompanied by lung involvement.

Isolation and identification of compounds with antinociceptive action from Ipomoea pes-caprae (L.) R. Br.

This study describes the isolation and identification of several constituents from Ipomoea pes-caprae (L.) R. Br., a medicinal plant frequently employed in folk medicine of many countries as a remedy against several diseases, including inflammation and pain. Our results demonstrate that some of these compounds, such as glochidone, betulinic acid, alpha- and beta-amyrin acetate, isoquercitrin, etc. showed pronounced antinociceptive properties in the writhing test and formalin test in mice. These data confirm our previous work concerning the antinociceptive action of the hydroalcoholic extract of I. pes-caprae and justify, at least in part, the popular use of this plant for the treatment of dolorous processes.

[Outpatient vaginal hysterectomy, feasibility and morbidity: an observational study on thirty patients]. / Étude observationnelle de la faisabilité et de la morbidité de l'hystérectomie vaginale ambulatoire: à propos de 30 cas.

OBJECTIVE: Outpatient surgery is nowadays a major evolution axis of the surgery in France. Outpatient vaginal hysterectomy is possible with the use of electrosurgical bipolar vessel sealing allowing the reduction of operative time and postoperative pain. Our aim was to study the feasibility and morbidity of outpatient vaginal hysterectomy by assessment of postoperative pain and satisfaction. PATIENTS AND METHODS: Thirty patients were enrolled in this observational study. All patients underwent an outpatient vaginal hysterectomy with a standardized operative technic. Pain was evaluated by administering a 10 cm visual analogic scale (VAS) at the first and second postoperative days. The total duration of analgesic treatment was noticed. Patient's satisfaction was recorded at the postoperative visit one month after the intervention and by a telephonic interview. RESULTS: The mean operative time was 59.3 (25-110) minutes and the mean uterine weight was 170.2 (60-710) grams. No intraoperative complications were reported. Among the thirty patients, 3 (10%) were not discharged the same day. At the first and second postoperative days, the VAS was 4.40 and 4.35 respectively. The mean total duration of analgesic's use was 5 days (3-8 days). Patients were very satisfied of medical care in 36.7% of cases (11/30), satisfied in 53.3% (16/30) and not much satisfied in 10% (3/30). In total, 83.3% (25/30) have agreed to repeat the procedure in the ambulatory sector. DISCUSSION AND CONCLUSION: Outpatient vaginal hysterectomy seems to be a possible and a safe technique with a high patient's satisfaction in France at the present time.

Placental fatty acid transport in maternal obesity.

Pregestational obesity is a significant risk factor for adverse pregnancy outcomes. Maternal obesity is associated with a specific proinflammatory, endocrine and metabolic phenotype that may lead to higher supply of nutrients to the feto-placental unit and to excessive fetal fat accumulation. In particular, obesity may influence placental fatty acid (FA) transport in several ways, leading to increased diffusion driving force across the placenta, and to altered placental development, size and exchange surface area. Animal models show that maternal obesity is associated with increased expression of specific FA carriers and inflammatory signaling molecules in placental cotyledonary tissue, resulting in enhanced lipid transfer across the placenta, dislipidemia, fat accumulation and possibly altered development in fetuses. Cell culture experiments confirmed that inflammatory molecules, adipokines and FA, all significantly altered in obesity, are important regulators of placental lipid exchange. Expression studies in placentas of obese-diabetic women found a significant increase in FA binding protein-4 expression and in cellular triglyceride content, resulting in increased triglyceride cord blood concentrations. The expression and activity of carriers involved in placental lipid transport are influenced by the endocrine, inflammatory and metabolic milieu of obesity, and further studies are needed to elucidate the strong association between maternal obesity and fetal overgrowth.

Micronutrients in pregnancy: current knowledge and unresolved questions.

Micronutrient status is increasingly recognized to play an important role in the health and well-being of pregnant women and in the development and long-term health of the offspring. On 26th - 28th February 2009, The Child Health Foundation invited leading experts in this area to a scientific workshop at Obergurgl, Austria to review and critically discuss current knowledge, to identify issues that may need to be addressed in future recommendations, and to highlight priorities and opportunities for future research. This report summarizes updated key conclusions of the workshop with regards to micronutrients' intake and physiological role related to mother, placenta and fetus, as well as relevance for adverse pregnancy and long-term outcomes.

Role of micronutrients in the periconceptional period.

BACKGROUND: Micronutrient deficiencies have been associated with significantly high reproductive risks, ranging from infertility to fetal structural defects and long-term diseases. In this review we focus on the reproductive risks related to some micronutrients during the periconceptional period, a critical step in determining fetal development and health due to the potential onset of several disorders. METHODS: Embase Medline and PubMed databases, Google-indexed scientific literature and periodics from on-line University of Milan Bibliotecary Service were searched to identify relevant publications. In vivo human studies were mainly searched for, but when needed animal studies as well as in vitro and cell culture experiments were also considered. RESULTS: Fertility, conception, implantation, fetal organogenesis and placentation are the critical stages potentially affected by nutrition during the periconceptional period. Reactive oxygen species (ROS) and total homocysteine (tHcy) plasma levels are factors involved in the respective mechanisms. The preconceptional period is particularly important since it affects both fertility and the early stages of gestation. Micronutrients' dietary intake and maternal status affect the different phases of the onset and development of pregnancy as well as of the conceptus. CONCLUSION: Although human studies are scarce, and conclusive evidence is provided solely for periconceptional folate and prevention of neural tube defects (NTDs), the overall data indicate that micronutrients may affects fertility, embryogenesis and placentation, and the prophylactic use of some micronutrients may be useful in preventing several adverse pregnancy outcomes. Efforts to increase awareness of a healthy diet should be strengthened not only throughout pregnancy but also before. However, further researches in humans are necessary to optimise periconceptional micronutrient requirements.