Berberine phospholipid exerts a positive effect on the glycemic profile of overweight subjects with impaired fasting blood glucose (IFG): a randomized double-blind placebo-controlled clinical trial.

OBJECTIVE: Berberine is a plant alkaloid known to exert positive metabolic effects. Human studies have confirmed its ability to improve the lipid and glycemic profile. This study aimed to evaluate the potential benefit of oral supplementation of Berberine PhytosomeTM (2 tablets/day, 550 mg/tablet) on the metabolic profile of subjects with impaired fasting blood glucose (IFG). PATIENTS AND METHODS: A total of 49 overweight subjects, 28 females and 21 males, were randomly assigned to either the supplemented group (n=24) or placebo (n=25). We considered glycemia as the primary endpoint and total cholesterol, high-density lipoprotein (HDL), total cholesterol/HLD, low-density lipoprotein (LDL), LDL/HDL, triglycerides, insulin, glycated hemoglobin, Homeostasis Model Assessment (HOMA), ApoA, ApoB, ApoB/ApoA, androgen suppression treatment (AST), alternative lengthening of telomeres (ALT), gamma-glutamyl transferase (GGT), creatinine, and body composition by dual-energy X-ray absorptiometry (DXA) as secondary endpoints. These parameters have been assessed at baseline, after 30 days, and after 60 days. RESULTS: After two months of treatment, through the use of linear mixed effect models, a statistically significant difference between supplemented and placebo groups was observed for glycemia [ß=-0.2495% C.I. (-0.47; -0.06), p=0.004], total cholesterol [ß=-0.25, 95% C.I. (-0.45; -0.04), p=0.05], total cholesterol/HDL [ß=-0.25, 95% C.I. (-0.43; -0.06), p=0.04], triglycerides [ß=-0.14, 95% C.I. (-0.25; -0.02), p=0.05], insulin [ß=-1.78, 95% C.I. (-2.87; -0.66), p=0.009], ApoB/ApoA [ß=-0.08, 95% C.I. (-0.13; -03), p=0.004], Visceral adipose tissue (VAT) [ß=-91.50, 95% C.I. (-132.60; -48.19), p<0.0001] and fat mass [ß=-945.56, 95% C.I. (-1,424.42; -441.57), p=0.004]. CONCLUSIONS: The use of berberine had no adverse events, supporting its use as a natural alternative to pharmacological therapies in the case of IFG.

An overview on the correlation between blood zinc, zinc intake, zinc supplementation and bone mineral density in humans.

INTRODUCTION: In case of zinc (Zn) deficiency, this mineral becomes a nutrient limiting muscle and bone synthesis. The study in humans on zinc and bone health are few and no reviews have been published on this topic. So, the aim of this narrative review was to consider the state of the art on the correlation between blood zinc, daily zinc intake, zinc supplementation and bone mineral density. MATERIAL AND METHODS: A narrative review was performed. RESULTS: This review included 16 eligible studies: eight studies concern Zn blood; three studies concern Zn intake and five studies concern Zn supplementation. CONCLUSION: Blood zinc levels seem to be lower in subjects with pathology related to bone metabolism. Regarding daily zinc intake, a high proportion of the population, more than 20%, seems to be at risk of having inadequate zinc intake. The literature suggests that an insufficient zinc intake (less than 3 mg/day) could be a risk factor for fractures and for development of osteopenia and osteoporosis. Zinc supplementation (40-50 g/day) could have beneficial effects on bone health in terms of maintaining bone mineral density and faster healing in the event of fractures, with even better results in situations of reduced intake zinc through food.

INTRODUCCIÓN: En caso de deficiencia de zinc, se limitará la síntesis muscular y ósea. Los estudios en humanos sobre zinc y salud ósea son pocos y no se han publicado comentarios sobre este tema. Por lo tanto, el objetivo de esta revisión narrativa es considerar el estado de la técnica sobre la correlación entre el zinc en la sangre, la ingesta diaria de zinc, la suplementación de zinc y la densidad mineral ósea. MATERIAL Y MÉTODOS: Se realizó una revisión narrativa. RESULTADOS: Esta revisión incluyó 16 estudios elegibles: ocho se refieren al zinc en sangre; tres estudios se refieren a la ingesta de Zn y cinco estudios se refieren a la suplementación de Zn. CONCLUSIÓN: Los niveles de zinc en sangre parecen ser más bajos en sujetos con patología relacionada con el metabolismo óseo. En cuanto a la ingesta diaria de zinc, una alta proporción de la población, más de 20%, parece estar en riesgo de tener una ingesta inadecuada de zinc. La literatura sugiere que una ingesta insuficiente de zinc (menos de 3 mg/día) podría ser un factor de riesgo de fracturas y para el desarrollo de osteopenia y osteoporosis. La suplementación con zinc (40-50 g/día) podría tener efectos beneficiosos sobre la salud ósea para mantener la densidad mineral ósea y una curación más rápida en caso de fracturas, con resultados aún mejores en situaciones de reducción de la ingesta de zinc a través de los alimentos.

An overview on the correlation between blood zinc, zinc intake, zinc supplementation and bone mineral density in humans / Una visión general sobre la correlación entre el zinc en la sangre, la ingesta de zinc, la suplementación de zinc y la densidad mineral ósea en los seres humanos

Abstract: Introduction: In case of zinc (Zn) deficiency, this mineral becomes a nutrient limiting muscle and bone synthesis. The study in humans on zinc and bone health are few and no reviews have been published on this topic. So, the aim of this narrative review was to consider the state of the art on the correlation between blood zinc, daily zinc intake, zinc supplementation and bone mineral density. Material and methods: A narrative review was performed. Results: This review included 16 eligible studies: eight studies concern Zn blood; three studies concern Zn intake and five studies concern Zn supplementation. Conclusion: Blood zinc levels seem to be lower in subjects with pathology related to bone metabolism. Regarding daily zinc intake, a high proportion of the population, more than 20%, seems to be at risk of having inadequate zinc intake. The literature suggests that an insufficient zinc intake (less than 3 mg/day) could be a risk factor for fractures and for development of osteopenia and osteoporosis. Zinc supplementation (40-50 g/day) could have beneficial effects on bone health in terms of maintaining bone mineral density and faster healing in the event of fractures, with even better results in situations of reduced intake zinc through food.

Resumen: Introducción: En caso de deficiencia de zinc, se limitará la síntesis muscular y ósea. Los estudios en humanos sobre zinc y salud ósea son pocos y no se han publicado comentarios sobre este tema. Por lo tanto, el objetivo de esta revisión narrativa es considerar el estado de la técnica sobre la correlación entre el zinc en la sangre, la ingesta diaria de zinc, la suplementación de zinc y la densidad mineral ósea. Material y métodos: Se realizó una revisión narrativa. Resultados: Esta revisión incluyó 16 estudios elegibles: ocho se refieren al zinc en sangre; tres estudios se refieren a la ingesta de Zn y cinco estudios se refieren a la suplementación de Zn. Conclusión: Los niveles de zinc en sangre parecen ser más bajos en sujetos con patología relacionada con el metabolismo óseo. En cuanto a la ingesta diaria de zinc, una alta proporción de la población, más de 20%, parece estar en riesgo de tener una ingesta inadecuada de zinc. La literatura sugiere que una ingesta insuficiente de zinc (menos de 3 mg/día) podría ser un factor de riesgo de fracturas y para el desarrollo de osteopenia y osteoporosis. La suplementación con zinc (40-50 g/día) podría tener efectos beneficiosos sobre la salud ósea para mantener la densidad mineral ósea y una curación más rápida en caso de fracturas, con resultados aún mejores en situaciones de reducción de la ingesta de zinc a través de los alimentos.

Sensorial strabismus due to congenital toxoplasmosis. Is it an eso- or exotropia?

OBJECTIVE: To examine sensorial strabismus due to congenital toxoplasmosis to elucidate differences and similarities between cases with esotropia (ET) and with exotropia (XT). METHODS: Restrospective analysis of 49 patients treated between 2002 and 2007. Visual acuity, cycloplegic refraction, strabismus patterns, presence of nystagmus, site of scar, surgery performed and strabismus surgical outcome obtained were evaluated. RESULTS: Mean age: 5 years old. 25 patients had bilateral involvement: 10 had ET, 10 XT and 4 were aligned. 15/24 unilateral cases presented with XT, 7 ET and other 2 orthotropia. 6/8 patients with the right eye affected, manifest ET and 14/16 patients with their OS affected had XT. (P=0.01) CONCLUSION: In bilateral cases of ocular toxoplasmosis ET and XT are found in similar proportions; in unilateral cases, XT is more frequent and the left eye is affected in most cases by both the toxoplasmosis and the strabismus. Esotropia appears more frequently in cases where the right eye is so affected, whereas XT predominates in cases where the left eye is affected.

The costs of epilepsy in Italy: a prospective cost-of-illness study in referral patients with disease of different severity.

PURPOSE: [corrected] Epilepsy poses a considerable economic burden on society. However, information is insufficient on the comparative costs of different disease varieties. The purpose of this study was to compare the direct costs of epilepsy in referral patients with disease of different severity and duration. METHODS: Patients with newly diagnosed epilepsy (NDE), seizure remission (SR), occasional seizures (OS), frequent non-drug-resistant (NDR) and drug-resistant (DR) seizures, and surgical candidates (SC) from 14 epilepsy centers were the target population. All patients were followed prospectively for 12 months and all medical and paramedical contacts for diagnostic and therapeutic services were noted with details, using ad-hoc diaries and semistructured questionnaires. RESULTS: The study population comprised 525 consecutive children and adults with partial (68%), generalized (25%) and undetermined epilepsy (4%) as follows: NDE 70; SR 131; OS 108; NDR 101; DR 107; SC 8. Ambulatory visits (mean 2.8 per patient per year) were the leading service in all groups, followed by EEG recordings (1.8) and biochemical assays (1.1). At entry, the commonest drugs were carbamazepine (50%), valproate (37%), phenobarbital (21%), vigabatrin (14%) and lamotrigine (11%). New antiepileptic drugs (AED) were used increasingly with the severity of the disease. The total annual costs varied significantly across groups: 3945 Euro (SC), 2198 Euro (DR), 1626 Euro (NDR), 1002 Euro (NDE), 558 Euro (OS), 412 Euro (SR). The main item of expenditure was hospital stay (including day-hospital), followed by drug treatment and outpatient visits. The costs of outpatient services, hospital services and drugs varied significantly across groups. CONCLUSIONS: The direct costs of epilepsy vary significantly depending on the severity of the disease and the response to treatment. Hospital admissions and drugs are the commonest items of expenditure.

Hypersomnia in the Prader Willi syndrome: clinical-electrophysiological features and underlying factors.

OBJECTIVE: Excessive daytime sleepiness is a common symptom in Prader Willi syndrome (PWs). Sleep disordered breathing (SDB) and narcoleptic traits such as REM sleep onsets (SOREMPs) have been reported in these subjects. We evaluated nighttime and daytime sleep patterns in patients with PWs in order to clarify the nature of their hypersomnia. DESIGN AND METHODS: We performed overnight continuous EEG-polysomnographic studies (with breathing monitoring included) in 14 subjects (6 M,8 F; mean age 17 years, range 8-37) affected by PWs unselected for sleep disturbances. Ten patients underwent a Multiple Sleep Latency Test (MSLT) the day following the nocturnal sleep studies. Patients assessment was completed by means of immunogenetic characterization. RESULTS: Nocturnal polysomnographic investigation documented sleep related breathing abnormalities such as central apneas, hypopneas or hypoventilation which mainly occurred during REM sleep in 8 subjects and did not cause sleep disruption. Only 4 subjects presented an increase in the Respiratory Disorder Index (RDI) slightly above the normal limits. In 8 subjects out of 10, with and without SDB, the mean daytime sleep latency could be considered abnormal according to the Tanner staging of pubertal development. Five patients showed at least two SOREMPs at MSLT. Subjects with and without SOREMPs had, respectively, a mean age of 18.6 SD 7.9 (4 M, 1 F) and 14.5 SD 2.9 (4 F, 1 M). The paternal deletion:uniparental dysomy ratio at genotypic characterization was 4:1 and 3.5:1 in subjects with and without SOREMPs, respectively. No patient presented DR-15 nor Dq-6. CONCLUSIONS: Excessive sleepiness is a frequent disturbance in PWs. Subgroups of PW patients show hypersomnolence and SOREMPs. Sleep disordered breathing appears to have a limited role in the genesis of hypersomnia which not seems on the other hand attributable to the coexistence of narcolepsy phenotype. Hypersomnia in PW syndrome is likely to mainly be attributable to a primary hypothalamic dysfunction. The potential interacting role of other factors such as subjects age, sex and genetic pattern is suggested and deserve further investigation.

Evaluation of sleepiness in epilepsy.

Excessive daytime sleepiness often complicates the clinical picture of epilepsy, facilitating the occurrence of seizures and aggravating cognitive disabilities and/or behavioral problems. Thus it further adversely affects social and working activities of epileptic subjects. Both unstructured and structured clinical reports documented a not negligible proportion of epilepsy patients suffering from excessive daytime sleepiness. Studies based on neurophysiological testing such as Multiple Sleep Latency Test or Maintenance Wakefulness Test revealed a degree of daytime sleepiness tendency in epilepsy patients greater than that they subjectively estimate. Antiepileptic drugs play a remarkable role in determining drowsiness in epilepsy patients and they are generally viewed as the only cause of sleepiness in these patients. However excessive daytime sleepiness has been documented in epilepsy patients before starting any drug treatment or after its discontinuation. Both clinical and neurophysiological studies have clearly documented the possible role of seizure occurrence and of co-morbidity as determinants of excessive daytime sleepiness in epilepsy patients. Nocturnal sleep fragmentation and daytime sleepiness have been reported in temporal lobe and frontal lobe epilepsy, namely nocturnal frontal lobe epilepsy. Some recent reports have stressed that obstructive sleep apnea and periodic limb movements during sleep can significantly account for sleepiness complaints in epilepsy patients; most of the antiepileptic drugs can worsen obstructive sleep apnea. To date the evaluation of daytime sleepiness of epilepsy patients in clinical practice has been based mainly or exclusively on clinical reports. To improve our understanding of this symptom in epilepsy patients, the use of standardized sleepiness scales should be encouraged. Patients with persistent daytime sleepiness without a clear cause-and-effect relationship with antiepiletic drugs treatment or in whom a coincident sleep pathology is suspected, should be investigated by means of neurophysiological testing such as Multiple Sleep Latency Test or Maintenance Wakefulness Test.

Sleep hygiene in adult epilepsy patients: a questionnaire-based survey.

Two hundred and seventy epilepsy patients referred to the Epilepsy Centre of the "C. Mondino" Institute of Neurology and 230 healthy subjects comparable for age, sex and education completed a sleep questionnaire of 112 multiple choice questions including those that concern sleep hygiene practice. The percentage of subjects with habitually inappropriate sleep hygiene habits was significantly higher in controls than in epilepsy patients for 7 out of the 9 sleep hygiene practices considered (P at chi square less than 0.05). No significant relationship between kind and/or severity of epilepsy and the degree of sleep hygiene practice was found. The data show that sleep hygiene practice is more adequate in epilepsy than in control subjects. It is possible that the appropriate sleep hygiene practice of epilepsy patients derives from the fact that they habitually refrain from a lot of practices which possibly aggravate both the course of epilepsy and seizure-related complications.

Epileptic skew deviation.

We describe a 43-year-old neurologically intact patient who reported episodes of diplopia and oscillopsia associated with a right-beating nystagmus and a skew deviation. These symptoms and signs were related to a left posterior epileptic EEG discharge. We suggest that these ocular motor signs derived from an ictal activation of the vestibular cortex, which in turn activated descending projections to the vestibular nuclei, leading to both a dynamic (right-beating nystagmus) and a static (skew deviation) vestibular imbalance.

Effects of valproate, phenobarbital, and carbamazepine on sex steroid setup in women with epilepsy.

Serum levels of sex-hormones, sex-hormone binding globulin, gonadotropin, and prolactin were evaluated during the follicular and the luteal phases in 65 women with epilepsy and in 20 healthy controls. Twenty-one patients were treated with sodium valproate (VPA), 21 with phenobarbital (PB), and 23 with carbamazepine (CBZ). VPA does not stimulate liver microsome enzymes, whereas PB and CBZ do. Patients on VPA therapy showed higher body weight and body mass index, but no significant differences in hirsutism score, or in ovary volume or polycystic ovary prevalence (at ultrasound examination). Estradiol levels were lower in all patient groups than in healthy controls in the follicular but not in the luteal phases. VPA affected luteal progesterone surge in 63.6% of cases. This effect was significantly lower in the CBZ and PB groups. Furthermore, increases in testosterone and delta 4-androstenedione levels and in free androgen index, along with a higher luteinizing hormone-follicle-stimulating hormone ratio in the luteal phase, were observed in women treated with VPA. Although sex-hormone binding globulin levels were higher in CBZ and PB than in VPA-treated patients, the differences were not significant because of the wide dispersion of the carrier protein levels. Inducer antiepileptic drugs decreased dehydroepiandrosterone sulfate levels, which remained unchanged during VPA treatment. No significant differences occurred in basal gonadotropin and prolactin levels.

Nocturnal eating: prevalence and features in 120 insomniac referrals.

Pathologic nocturnal eating can be associated with a heterogeneous group of medical and psychiatric disorders. The current study was designed to evaluate the prevalence and clinical features of nocturnal eating syndrome (NES), a major subtype of pathological nocturnal eating. Conducted prospectively over an 18-month period (January 1994-June 1995), the study consisted of clinical, psychological, and polysomnographic assessments of 120 adult subjects (51 males, 69 females; mean age 42.6 years, range 18-86 years) who were either self-referrals (58%) or physician referrals (42%) to our Sleep Disorders Center for insomnia complaints. Nocturnal eating with features that are typical of NES, namely compulsive feeding shortly after a mid-non-rapid eye movement (NREM) sleep awakening, in the absence of daytime eating disorders, occurred in seven subjects (five females, two males; mean age 50.8 +/- 9.5 years; mean age at onset of NES 42 years, range 18-61 years), or 5.8% of the sample. NES accounted for 44.4% of all the nocturnal eating cases observed. The data suggest that an adult, late-onset variety of NES is not infrequent. Several of the clinical features of our NES patient series correspond closely to most of those observed in other descriptions of NES in the literature. Overall, the data reinforce the idea that NES is a distinct syndrome, even though some of its features overlap with sleep-related eating disorders (e.g. associated with sleepwalking, restless legs syndrome, obstructive sleep apnea, etc.) and with eating disorders such as daytime binge eating.

Menstrual cycle and ovary alterations in women with epilepsy on antiepileptic therapy.

Impaired reproductive function is thought to frequently affect women with epilepsy, mainly when seizures originate in the temporal lobe. In this study, we evaluated menstrual cycle features and assessed ovulation by determining luteal progesterone (Pg) levels in 101 consecutive women with epilepsy (36 with idiopathic generalized epilepsy -IGE; 65 with partial epilepsy -PE), aged between 16 and 50 years, treated with various antiepileptic drugs (AED). PE originated in the temporal lobe (TLE) in 40 subjects, in the frontal lobe in 13, in the parietal lobe in 2, while the origin of focal seizures remained undetermined in 10 patients. In all patients, menstrual and reproductive history, body mass index, hair distribution and hormonal pattern were assessed. Suprapubic ovary ultrasound (US) examination was carried out in 83 patients (28 with IGE, 55 with PE). Three patients with IGE and one with PE were amenorrheic. Oligomenorrhea occurred in 16 patients, polymenorrhea in 2. Changes in menstrual cyclicity were independent from epilepsy type (19.4% in IGE; 23.1% in PE) and from origin of focal discharges (22.5% of patients with TLE; 20.0% with origin in other brain areas). Luteal Pg levels remained below 2 ng/ml in 30 patients independently of epilepsy type. Corpus luteum dysfunction was combined with hyperandrogenism in 15 of these patients. In the other cases different alterations of hypothalamus-pituitary-ovary axis were observed. Valproic acid blunted luteal Pg surge more frequently than other AED. Polycystic ovaries (PCO) were observed in 14 (16.9%) patients (21.0% with IGE: 14.5% with PE). These prevalences are not higher than those reported in the general population. Among PE patients, PCO was found in 1 case with undetermined focal origin and in 7 TLE cases, who also had ovary volume significantly larger than patients with seizures originating from the frontal or parietal lobe. Epileptic women exhibited an increased occurrence of multifollicular ovaries (MFO) found in 12 cases (14.4% vs 5% in the general population). However, no defined hormonal or clinical pictures were associated with this US alteration in most patients. These findings reappraise the impact of ovary alterations in women mainly affected by mild to moderate epilepsy, on differing AED regimens, with the exception of more frequent ovulatory dysfunction and PCO occurrence in patients taking VPA.

Carbamazepine affects neutrophil function through an action on peripheral benzodiazepine receptors.

The aims of this study were to assess the possible role of peripheral benzodiazepine receptors (pBZrs)1 in mediating the in vitro effects of carbamazepine (CBZ) on some neutrophil functions in healthy volunteers and to investigate neutrophil function and pBZr expression in patients with epilepsia on CBZ monotherapy for at least 1 year. In vitro CBZ (42-168 microM) concentration-dependently inhibited chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or lipopolysaccharide (LPS)-activated human serum. CBZ did not affect random migration, phagocytosis index, phagocytosis frequency, NBT reduction frequency, C. albicans lethality index and resting superoxide production. The pBZr antagonist PK 11195 (1 microM, per se ineffective) reversed the inhibitory effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP. The pBZr agonist Ro 5-4864 (10-100 microM) mimicked the effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP and had no effect on the other parameters. Neutrophils from epileptic patients on chronic CBZ monotherapy had impaired FMLP- and serum-induced chemotaxis and enhanced expression of pBZrs on neutrophils. These data strongly suggest an involvement of pBZrs in mediating the in vitro effects of CBZ on chemotaxis; furthermore, impairment of the same neutrophil function parameters and overexpression of pBZrs in patients are consistent with the hypothesis of an in vivo interaction of CBZ with pBZrs.

Nocturnal partial seizures and arousals/awakenings from sleep: an ambulatory EEG study.

The architecture of nocturnal sleep in twenty subjects (9 males, 11 females, mean age 27 years) affected by partial cryptogenic epilepsy was investigated by means of ambulatory EEG (A-EEG) recording performed at home. The study aimed in particular to ascertain the immediate effects of nocturnal partial epileptic seizures on sleep stability and continuity. Data for a total of 49 recorded seizures indicate that 72% of the partial seizures which occurred during sleep were followed by arousal and awakening, and that sleep interruption lasted significantly longer when the seizure occurred between 4 and 7 a.m.

Poor sleep in adolescents: a study of 869 17-year-old Italian secondary school students.

Subjective sleep quality and its related factors were investigated in 869 (530 F, 339 M) 17-year-old adolescents, who were selected from the pupils of state-run secondary schools in the city of Pavia in the north west of Italy. The study was conducted cross sectionally, and it consisted of a questionnaire based survey. One hundred and forty-two subjects (16.5% of the whole sample, 19% of the females and 11.7% of the males) met the criteria chosen for definition as poor sleepers (namely, a complaint of 'non restorative nocturnal sleep', 'often' or 'always' over the previous 12 mo). A significant association was found between chronic poor sleep and (1) gender (female) (2) emotional factors, such as worries, anxiety and depression (3) poor sleep hygiene (4) arousal related parasomnia. Only 4% of poor sleepers took sleep promoting drugs (including benzodiazepines, homeopathic products and other medications), generally without seeking medical advice.

Efficacy and safety of topiramate in refractory epilepsy: a long-term prospective trial.

The effects of topiramate in 15 patients with drug refractory epilepsy or Lennox-Gastaut syndrome were assessed in an open, add-on prospective study. After a follow-up of 14-21 months, six patients are still on topiramate (mean dosage 583 mg/day, range 400-800 mg/day), and nine have discontinued treatment because of adverse events (n = 6), inefficacy (n = 2) or poor compliance (n = 1). Nine patients (69%) continued to have > or = 50% reduction in seizure frequency during the last two months of treatment, and one has been seizure-free for the last 19 months. The most common adverse events were somnolence, weight loss, mental slowing, fatigue, ataxia and irritability. Most of these events were reversible, but withdrawal of treatment was required in six cases as a result of ataxia (two patients), somnolence, metabolic acidosis, irritability or psychotic symptoms (one patient each). It is concluded that topiramate is a valuable agent for long-term management of refractory epilepsy.