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.

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.

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.

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.

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.

Electroencephalographic and autonomic effects of centrally administered dermorphin in rabbits.

Dermorphin, administered into the third ventricle of conscious rabbits, induces an increase of the total power density spectrum of the cortex and a decrease of the total power of the hippocampus. The electrocortical pattern is similar to that found with other opiates and reported as specific of mu agonists. Simultaneously the peptide causes respiratory depression, bradycardia and hypothermia. Naloxone (0.5 mg/kg IV) quickly and completely inverts all these effects. The activity of serotoninergic, Gabaergic, catecholaminergic and cholinergic systems does not seem to be required for these dermorphin actions. Thus, the hypothesis that dermorphin acts directly in modifying cerebral electrical activity is put forward.

Neuropeptides and cerebral electric activity in rabbits.

The effects of some neuropeptides infused into the cerebral ventricles on the spontaneous cerebral electric activity were studied in unanasthetized rabbits. The following peptides were investigated: physalaemin, caerulein, bombesin, litorin (supplied by Farmitalia). The rabbits were prepared according to Monnier and Gangloff's [10] method in order to record the spontaneous cortical activity. Each of these substances affects the electroencephalographic (EEG) records in a specific and dose-related way. Bombesin induces a biphasic pattern (synchronization followed by a partial activation), litorin is partially activating and physalaemin brings about a marked desynchronization. In spite of the marked structural analogy between bombesin and litorin, their EEG effects differ.

Centrally administered N-terminal fragments of ACTH (1-10, 4-10, 4-9) display convulsant properties in rabbits.

Electroencephalographic and behavioral effects of the following ACTH fragments: 1-4, 4-9, 4-11, 1-10, 4-10, 1-13, 1-17 and 1-24 were studied in rabbits. Sequences 4-9, 1-10 and 4-10 displayed some epileptic properties, i.e., they induced epileptic seizures (only electrographic or also behavioral) or increased hippocampal spiking. The 4-9 sequence seemed to be the common sequence responsible for these proconvulsant effects. The possible involvement of the enkephalinergic system is discussed.

Synchronizing, sedative and anticonvulsive effects of centrally administered somatostatin in the conscious rabbit.

The effects of intracerebroventricular injection of somatostatin-14 on the cortical and deep structure electrical activity, somatic behavior and rectal temperature, were studied in 45 unanesthetized rabbits. In addition the antiepileptic action of the peptide was tested in these models: pentamethylenetetrazole-induced cortical spikes and waves, epileptic focus by topical application of strychnine and voltage-threshold for amygdala after-discharge. The results indicate that somatostatin exerts synchronizing, sedative and weak antiepileptic effects when centrally administered to rabbits.

Breathing patterns and HbSaO2 changes during nocturnal sleep in patients with Duchenne muscular dystrophy.

A night-time polygraphic sleep recording with continuous HbSaO2 monitoring was performed in 11 chair-bound Duchenne muscular dystrophy patients with severe restrictive lung disease but with blood gas values within normal limits when awake. No abnormalities of sleep pattern were detected. Nocturnal sleep did not have significant adverse effects on respiration. However, in 6 patients, infrequent central apnoeas or hypopnoeas occurred which were associated with falls in HbSaO2 greater than those that have been reported to be in normal subjects. The magnitude of HbSaO2 falls appeared to be significantly correlated with functional residual capacity values. Overall, the findings revealed a relatively preserved, although unstable, blood O2 balance during nocturnal NREM and REM sleep in patients with Duchenne muscular dystrophy, even in an advanced stage of their illness.

A clinical, EEG and CT study in 21 cases of chronic respiratory failure.

A clinical, EEG and CT study was carried out on 21 patients with chronic stable respiratory failure. The neurological disturbances and mental deterioration observed were of a mild degree, and no severe alterations were detected at EEG. CT showed cerebral atrophy, but the type and prevalence did not differ substantially between patients studied and normal sex- and age-matched control subjects. The data gave evidence that in chronic stable respiratory failure cerebral function is only slightly affected.

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.

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.

The spectrum of actions of thyrotropin-releasing hormone on the CNS: a polygraphic study on rabbits.

The effects of i.c.v. administered thyrotropin-releasing hormone (TRH) on EEG, rectal temperature and behaviour were studied on rabbits in basal conditions and after different pretreatments. The effects of TRH on the EEG and behaviour do not seem to involve serotoninergic, catecholaminergic and cholinergic systems. A possible involvement of the GABAergic system is hypothesized.

Sleep patterns in patients with late onset partial epilepsy receiving chronic carbamazepine (CBZ) therapy.

A night-time polygraphic sleep recording was performed in 14 patients with late onset partial epilepsy receiving chronic carbamazepine monotherapy. All patients had unstable nocturnal sleep patterns as indicated by significantly altered sleep continuity parameters compared with normal controls. Patients with poor seizure control tended to show greater alterations of sleep stability compared to patients in complete clinical remission but the difference failed to reach statistical significance. Epileptic patients also showed less REM sleep and longer REM latencies compared with normal controls, the most altered REM values being observed in patients with poor seizure control. These data confirm that polygraphic sleep alterations are seen in patients with symptomatic focal epilepsy and indicate that these abnormalities occur irrespective of seizure recurrence.

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.

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.

Daytime sleepiness in epileptic patients on long-term monotherapy: MSLT, clinical and psychometric assessment.

A multiparametric investigation of daytime sleepiness was carried out in 10 patients with a generalized epilepsy treated by phenobarbital, 10 with a cryptogenic partial epilepsy treated by carbamazepine and 10 healthy controls. After a standard ambulatory night-time polysomnography, an objective and subjective estimate of daytime sleepiness was made in each subject by means of the Multiple Sleep Latency Test (MSLT) and visual analogue rating scale (VARS), respectively. Furthermore, a parallel assessment of mood and cognitive tasks involving attention and psychomotor speed was also carried out. The data show that patients on chronic treatment with phenobarbital have a greater daytime sleep tendency and they show a worse score at the digit symbol substitution test, than patients on carbamazepine and healthy controls.

Drug withdrawal in patients with epilepsy: prognostic value of the EEG.

The role of the inter-ictal EEG in predicting seizure relapse after antiepileptic drug withdrawal (AED-W) is unclear. A prospective study on AED-W is in progress. This trial includes routine and sleep EEG recordings every 3 and 6 months, respectively, at each step of the drug discontinuation and periodically during follow-up. Data obtained for 136 patients (mean age 23.2 years; 63 with Idiopathic Generalized Epilepsy IGE, 73 with Partial Cryptogenic or Symptomatic Epilepsy PE; without associated neuropsychiatric handicap; with at least 1 year of follow-up after AED-W) were analysed. EEG recordings from seizure onset were available for all patients. Data were analysed separately in IGE and PE patients. The presence of inter-ictal epileptiform abnormalities (IEAs) at the seizure onset and just before AED-W does not seem to predict the AED-W outcome. However, results indicate an association between persisting and increased IEAs during AED-W and a higher relapse rate in both groups, which was statistically significant in the IGE patients.