Interventions for sleep difficulties in adults with an intellectual disability: a systematic review.

BACKGROUND: Current literature highlights higher prevalence rates of sleep difficulties amongst adults with an intellectual disability. However, no synthesis has been conducted to assess the effectiveness of existing interventions in this population. Thus, the aim of this review was to assess the effectiveness of sleep interventions in adults with an intellectual disability (ID). METHOD: Eight databases were searched to identify interventions for sleep difficulties amongst adults with an ID. The study quality was assessed with the Risk Of Bias In Non-randomised Studies - of Interventions. Nine studies (n = 97) were eligible for inclusion in the review. RESULTS: There was a notable study on heterogeneity in terms of the population, study design, intervention studied, sleep assessment and outcome assessments used. Eight of the nine studies reported improvement in sleep following intervention. However, these findings need additional support as only 97 participants involving a variety of interventions and measurement systems were used across all studies. Furthermore, eight of the nine studies had serious to critical risk of bias. The only study identified as having low risk of bias was a placebo-controlled randomised controlled trial for the use of melatonin. CONCLUSIONS: This review highlights the need for objective measures such as actigraphy and studies with greater experimental control investigating sleep interventions in adults with ID.

Surgical management of colonic basidiobolomycosis among adolescent and adult patients: presentation and outcome.

AIM: The aim of this study was to review retrospectively the clinical presentations, indications for surgery and surgical outcomes of adolescent and adult patients who were diagnosed with colonic basidiobolomycosis in the last 10 years. METHOD: The study was carried out in Aseer Central Hospital, Abha, Saudi Arabia by reviewing the medical files of all patients in the last 10 years who were diagnosed with colonic basidiobolomycosis and required surgical intervention. RESULTS: There were 22 patients. Common findings in all patients were weight loss, abdominal pain and an abdominal mass. The right colon was affected in 21 patients. The initial diagnosis was correct in seven patients while nine were thought to be malignant. All patients underwent colonic resection followed by at least 1 year of antifungal medical treatment. Intra-operatively, all patients had moderate or dense adhesions, an abdominal mass and lymphadenopathy. Most surgeons had the impression intra-operatively that the diagnosis was inflammatory rather than malignant. Postoperatively, three patients died within 6 months of the operation due to progression of the disease. Four patients developed severe wound infections, three of whom had abdominal dehiscence and required re-closure. CONCLUSION: Colonic basidiobolomycosis is a life-threatening fungal infection that should be considered a surgical condition. A high index of suspicion including basidiobolomycosis in the differential diagnosis for the acute abdomen with a colonic mass is required for a proper diagnosis. Early aggressive surgical management followed by a prolonged course of itraconazole postoperatively could improve the outcome of the condition.

Personalized medicine approaches in epilepsy.

Epilepsy affects 50 million persons worldwide, a third of whom continue to experience debilitating seizures despite optimum anti-epileptic drug (AED) treatment. Twelve-month remission from seizures is less likely in female patients, individuals aged 11-36 years and those with neurological insults and shorter time between first seizure and starting treatment. It has been found that the presence of multiple seizures prior to diagnosis is a risk factor for pharmacoresistance and is correlated with epilepsy type as well as intrinsic severity. The key role of neuroinflammation in the pathophysiology of resistant epilepsy is becoming clear. Our work in this area suggests that high-mobility group box 1 isoforms may be candidate biomarkers for treatment stratification and novel drug targets in epilepsy. Furthermore, transporter polymorphisms contributing to the intrinsic severity of epilepsy are providing robust neurobiological evidence on an emerging theory of drug resistance, which may also provide new insights into disease stratification. Some of the rare genetic epilepsies enable treatment stratification through testing for the causal mutation, for example SCN1A mutations in patients with Dravet's syndrome. Up to 50% of patients develop adverse reactions to AEDs which in turn affects tolerability and compliance. Immune-mediated hypersensitivity reactions to AED therapy, such as toxic epidermal necrolysis, are the most serious adverse reactions and have been associated with polymorphisms in the human leucocyte antigen (HLA) complex. Pharmacogenetic screening for HLA-B*15:02 in Asian populations can prevent carbamazepine-induced Stevens-Johnson syndrome. We have identified HLA-A*31:01 as a potential risk marker for all phenotypes of carbamazepine-induced hypersensitivity with applicability in European and other populations. In this review, we explore the currently available key stratification approaches to address the therapeutic challenges in epilepsy.

Plasma cell-rich acute rejections in living-related kidney transplantation: a clinicopathological study of 50 cases.

BACKGROUND: Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcomes. PATIENTS AND METHODS: Between February 2012 and December 2013, 1630 dysfunctional renal graft biopsies were performed. Of these, 50 (3%) showed PCAR. ARs with >10% plasma cells were defined as PCAR. Human leukocyte antigen (HLA) antibodies were tested in historic sera and at the time of PCAR. Treatment for PCAR comprised methylprednisolone, antithymocyte globulin, plasmapheresis, and anti-CD20 antibody. RESULTS: Of the 1630 dysfunctional biopsies, 50 (3%) had PCAR which occurred 3.1 ± 2.55 yr after transplant. The percentage of plasma cells was 28.8 ± 11.7, and CD138, 29.0 ± 12.4. Donor-specific antibodies (DSAs) were found in 32 (64%) overall, Class I in 15% and Class II in 65%. Post-treatment serum creatinine improved from 3.80 ± 2.59 to 2.66 ± 1.59 mg/dL in DSA positive (p < 0.003) and from 2.59 ± 1.09 to 2.08 ± 0.86 mg/dL in DSA negative (p < 0.008). One- and two-yr graft survival after PCAR was 72%, 42% in the DSA-positive vs. 89%, 82% in the DSA-negative group, respectively (p = 0.071). CONCLUSIONS: Our results show that PCAR occurs late after transplant and in many cases is associated with DSAs. Graft outcome was poor when PCAR was associated with DSAs.

Rheology of saliva in health and disease.

BACKGROUND: Saliva is a complex fluid that lubricates the oropharynx and facilitates chewing, swallowing, and vocalization. Viscoelasticity is critical for the ability of saliva to fulfill these functions. Xerostomia, or a sensation of dry mouth, occurs in 17-26% of the population. Although many equate xerostomia with hyposalivation, high-risk patients frequently report oral dryness in the absence of decreased salivary flow. OBJECTIVE: This study aims to determine if xerostomia is associated with alterations in the rheological properties of saliva in addition to decreased salivary production. METHODS: The study population included patients with post-radiation xerostomia, patients with anticholinergic-induced xerostomia and healthy controls. Salivary volumetric flow rate was measured, shear viscosity was measured using oscillatory rheometry, and extensional viscosity was measured using capillary thinning methods. Groups were compared using descriptive statistics and univariate analysis. RESULTS: A total of 36 subjects were included: 15 with post-radiation xerostomia, 9 with anticholinergic-induced xerostomia and 12 controls. Salivary volumetric flow was significantly decreased in post-radiation and anticholinergic-induced patients compared to controls. On capillary thinning testing, saliva from xerostomia patients had significantly greater extensional viscosity compared to controls. However, saliva from the three groups showed no significant difference in the complex viscosity or the storage or loss modulus of saliva with oscillatory rheology. CONCLUSIONS: Xerostomia is associated with decreased salivary volumetric flow and quantitative changes in the rheologic properties of saliva.

Role of Mifepristone in Trial of Labour after Previous Caesarean Delivery in Intrauterine Fetal Death.

When a baby dies in utero, the options are either to wait for spontaneous labour or to induce it. An obstetrician, encounters with a perplexity of choosing a management plan when this worst situation of IUFD coalesced by history of previous caesarean delivery. The ideal drug for the termination should not only be efficacious and cost-effective, but also be convenient enough to avoid operative interference arising from a wasted pregnancy. The study was aimed to evaluate efficacy, safety and compliance of oral mifepristone in trial of labour in case of IUFD after previous caesarean section. This was a cross sectional descriptive type of observational study conducted in the Department of Obstetrics and Gynaecology, Mymensingh Medical College Hospital, Bangladesh from February 2018 to August 2018. Total 50 patients were selected purposively based on inclusion criteria and diagnosed as IUFD with previous caesarean delivery. The patients were received mifepristone once and reviewed after 48 hours and those who were not attained favourable Bishop's score were counseled for mechanical induction. Antibiotics and analgesia were administered according to requirement. Data analysis was done using SPSS version 22.0. All the 50 women received 200 mg oral mifepristone. Forty-four 44(88.0%) women was delivered vaginally among them 18(36.0%) were delivered following mifepristone induction only and 26(52.0%) required additional induction method. The earliest induction to delivery interval following mifepristone was 13 hours. Twenty eight (63.6%) cases were discharged within 72-120 hours. After 48 hours following induction there was significant improvement of Bishop's score. In this study 6(12.0%) out of 50 cases were reasoned for laparotomy and blood transfusion was required for them. There was no statistically significant difference according to gestational age in mode of delivery (p>0.05). There was no difference observed in mean induction to delivery interval between second and third trimester at 5% level of significance (p>0.05). In this study, the women showed drastic improvement in cervical score following induction with mifepristone and decreased repeat caesarean rate. Eventually, the length of agony of receiving dead baby was cut short without much more ailments. Hence, mifepristone may be considered as a safe, efficacious, convenient and cost-effective induction agent for labour induction in women with dead fetus in utero in previously scarred uterus.

Current intraoperative devices to reduce visual loss after spine surgery.

Postoperative visual loss (POVL) after spine surgery performed with the patient prone is a rare but devastating postoperative complication. The incidence and the mechanisms of visual loss after surgery are difficult to determine. The 4 recognized causes of POVL are ischemic optic neuropathy (approximately 89%), central retinal artery occlusion (approximately 11%), cortical infarction, and external ocular injury. There are very limited guidelines or protocols on the perioperative practice for "prone-position" surgeries. However, new devices have been designed to prevent mechanical ocular compression during prone-position spine surgeries. The authors used PubMed to perform a literature search for devices used in prone-position spine surgeries. A total of 7 devices was found; the authors explored these devices' features, advantages, and disadvantages. The cause of POVL seems to be a multifactorial problem with unclear pathophysiological mechanisms. Therefore, ocular compression is a critical factor, and eliminating any obvious compression to the eye with these devices could possibly prevent this devastating perioperative complication.

Clinical and Demographic Predictor of the Advanced Stage of Carcinoma Cervix in a Tertiary Level Hospital of Bangladesh.

Though cervical cancer is a preventable disease it is the most progressive and devastating diseases posing a threat of mortality for women of developing countries. Majority of the cases present to hospital at advanced stage when treatment is less feasible. Objective is to determine the factors associated with the advanced stage presentation to the hospital, socio-demographic factor, patterns of complications and histological types among patients with carcinoma cervix. This was an observational descriptive type of cross-sectional study carried out in the department of Obstetrics and Gynecology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from 15 January to 27 September 2017. Women who were newly confirmed to have cervical cancer by histology were enrolled. Stages IIB and above was considered as advanced disease. The patients were interviewed face to face by the researcher for the purpose of collection of data. Then the patients were examined by the researcher for certain sings and those would be recorded in the check-list. Histopathological report was noted in data collection sheet. In this study data analysis was done by SPSS version 22.0. Total 66 clinically and histologically confirmed advanced ca-cervixes were taken up during this study. Most common stage was stage III, 49(74.2%) out of 66 population. Majority of female were found 34(51.5%) in age group 51-60. More than half of population 54(81.8%) were living with their husband and 12(18.1%) were widow at the time of study. High level of illiteracy among women and their problematic health seeking behavior for gynecological symptoms are responsible for advanced diagnosis of cervical cancer.

Polymorphic Hh genes in the HLA-B(C) region control natural killer cell frequency and activity.

We demonstrated earlier that individuals homozygous for conserved major histocompatibility complex (MHC)-extended haplotypes have low natural killer (NK) activity as measured by cytolysis of the K562 tumor cell lines. In the present study, we investigated the segregation and MHC linkage of NK activity in families in which MHC haplotypes of human histocompatibility leukocyte antigens (HLA)-A, -C, and -B, complotype, and DR specificities are known. In two informative families, low activity was inherited as a recessive trait linked to the MHC. By using individuals homozygous for specific fragments of extended haplotypes or for HLA-B alleles, we found that the HLA-C and -B and not the complotype or HLA-DR region contains genes controlling NK activity. The majority of the unrelated individuals with low NK activity were homozygous or doubly heterozygous for HLA-B7 (Cw7), B8 (Cw7), B44 (Cw5), B18, or B57 (Cw6). Thus, these alleles form one complementation group designated NKB1. Another less frequent group, NKB2, was also identified, and consisted of individuals homozygous for B35 (Cw4). NK activity was correlated with the number of circulating NK (CD16+ CD56+) cells. Individuals homozygous for the NKB complementation groups have fewer circulating NK cells than individuals heterozygous for these alleles and alleles of other complementation groups, possibly explaining the low activity of cells in these subjects. These findings suggest that during the maturation of NK cells there is NK cellular deletion in donors homozygous for NKB genes resulting in low NK cell numbers and activity.

Linkage of pemphigus vulgaris antibody to the major histocompatibility complex in healthy relatives of patients.

Pemphigus vulgaris (PV) is an autoimmune disease caused by high concentrations of antibody to an epidermal cadherin. The disease is associated with two kinds of HLA-DR4, DQ8 haplotypes dominantly distributed among Jewish patients, and these plus DR6, DQ5 haplotypes in non-Jewish patients. Low levels of the PV antibody were found in 48% of a total of 120 asymptomatic parents, children, and siblings of 31 patients, thus exhibiting dominant inheritance. The inheritance of these low levels of antibody in asymptomatic relatives was linked to the major histocompatibility complex with a highly significant logarithm of the odds score of 9.07, almost always to a DR4 or DR6 haplotype of the patient. Disease appears to occur in susceptible individuals with low levels of antibody when a second factor, either environmental or genetic, induces high levels, sufficient to produce blisters.

Laryngeal tremor: co-occurrence with other movement disorders.

INTRODUCTION: Limited epidemiologic information exists regarding the co-occurrence of laryngeal tremor (LT) and tremor in other parts of the body, and of other movement disorders. Tremor is the involuntary skeletal muscle contraction that leads to oscillatory movement. It can affect many parts of the body including the chin, neck, laryngeal muscles, or limbs. When it is not associated with parkinsonism, it is called an essential tremor. We reviewed our 5-year experience with LT patients and the presence of other movement disorders. METHODS: We performed a retrospective review of 29 patients with LT seen in a voice clinic over a 5-year period from January 2004 to April 2009. RESULTS: Of the 29 patients, 27 (93%) had co-incidence of another movement disorder. Of these patients, 45% had spasmodic dysphonia, 41% had oropharyngeal tremors, 38% had essential limb tremor, 31% had orofacial dystonias, and 24% had essential head and neck tremor. Only 1 patient (3%) presented with Parkinson's disease. CONCLUSION: Otolaryngologists may be the first to evaluate a patient for tremors. It is important to consider other movement disorders when examining these patients as neurologic assessment and treatment of other tremors may be beneficial.

Human olfactory epithelial cells generated in vitro express diverse neuronal characteristics.

The olfactory epithelium constitutes the sole source of regenerating neural cells that can be obtained from a living human. As such, primary cultures derived from human olfactory epithelial biopsies can be utilized to study neurobiological characteristics of individuals under different conditions and disease states. Here, using such human cultures, we report in vitro generation of cells that exhibit a complex neuronal phenotype, encompassing receptors and signaling pathways pertinent to both olfaction and other aspects of CNS function. Using in situ hybridization, we demonstrate for the first time the native expression of olfactory receptors in cultured cells derived from human olfactory epithelial tissue. We further establish the presence and function of olfactory transduction molecules in these cells using immunocytochemistry, calcium imaging and molecular methods. Western blot analysis revealed the expression of neurotransmitter receptors for dopamine (D2R), 5-HT (5HT2C) and NMDA subtypes 1 and 2A/2B. Stimulation with dopamine or 5-HT enhanced receptor G protein activation in a subtype specific manner, based on 35S-guanosine triphosphate incorporation assay. Functional characteristics of the cultured cells are demonstrated through enhanced tyrosine phosphorylation of NMDAR 2A/2B and recruitment of signaling partners in response to NMDA stimulation. The array of neuronal characteristics observed here establishes that proliferating cells derived from the human olfactory epithelium differentiate in vitro to express functional and molecular attributes of mature olfactory neurons. These cultured neural cells exhibit neurotransmitter pathways important in a number of neuropsychiatric disorders. Their ready availability from living humans thus provides a new tool to link functional and molecular features of neural cells with clinical characteristics of individual living patients.

Comparison of the novel subtype-selective GABAA receptor-positive allosteric modulator NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain.

Spinal administration of GABA(A) receptor modulators, such as the benzodiazepine drug diazepam, partially alleviates neuropathic hypersensitivity that manifests as spontaneous pain, allodynia, and hyperalgesia. However, benzodiazepines are hindered by sedative impairments and other side effect issues occurring mainly as a consequence of binding to GABA(A) receptors containing the alpha(1) subunit. Here, we report on the novel subtype-selective GABA(A) receptor-positive modulator NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], which possesses a functional efficacy selectivity profile of alpha(5) > alpha(3) > alpha(2) > alpha(1) at GABA(A) alpha subunit-containing receptors. Oral administration of NS11394 (1-30 mg/kg) to rats attenuated spontaneous nociceptive behaviors in response to hindpaw injection of formalin and capsaicin, effects that were blocked by the benzodiazepine site antagonist flumazenil. Ongoing inflammatory nociception, observed as hindpaw weight-bearing deficits after Freund's adjuvant injection, was also completely reversed by NS11394. Likewise, hindpaw mechanical allodynia was fully reversed by NS11394 in two rat models of peripheral neuropathic pain. Importantly, NS11394-mediated antinociception occurred at doses 20 to 40-fold lower than those inducing minor sedative or ataxic impairments. In contrast, putative antinociception associated with administration of either diazepam, zolpidem, or gaboxadol only occurred at doses producing intolerable side effects, whereas bretazenil was completely inactive despite minor influences on motoric function. In electrophysiological studies, NS11394 selectively attenuated spinal nociceptive reflexes and C-fiber-mediated wind-up in vitro pointing to involvement of a spinal site of action. The robust therapeutic window seen with NS11394 in animals suggests that compounds with this in vitro selectivity profile could have potential benefit in clinical treatment of pain in humans.

NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a unique subtype-selective GABAA receptor positive allosteric modulator: in vitro actions, pharmacokinetic properties and in vivo anxiolytic efficacy.

The novel positive allosteric modulator NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] possesses a functional selectivity profile at GABA(A) receptors of alpha(5) > alpha(3) > alpha(2) > alpha(1) based on oocyte electrophysiology with human GABA(A) receptors. Compared with other subtype-selective ligands, NS11394 is unique in having superior efficacy at GABA(A)-alpha(3) receptors while maintaining low efficacy at GABA(A)-alpha(1) receptors. NS11394 has an excellent pharmacokinetic profile, which correlates with pharmacodynamic endpoints (CNS receptor occupancy), yielding a high level of confidence in deriving in vivo conclusions anchored to an in vitro selectivity profile and allowing for translation to higher species. Specifically, we show that NS11394 is potent and highly effective in rodent anxiety models. The anxiolytic efficacy of NS11394 is most probably mediated through its high efficacy at GABA(A)-alpha(3) receptors, although a contributory role of GABA(A)-alpha(2) receptors cannot be excluded. Compared with benzodiazepines, NS11394 has a significantly reduced side effect profile in rat (sedation, ataxia, and ethanol interaction) and mouse (sedation), even at full CNS receptor occupancy. We attribute this benign side effect profile to very low efficacy of NS11394 at GABA(A)-alpha(1) receptors and an overall partial agonist profile across receptor subtypes. However, NS11394 impairs memory in both rats and mice, which is possibly attributable to its efficacy at GABA(A)-alpha(5) receptors, albeit activity at this receptor might be relevant to its antinociceptive effects (J Pharmacol Exp Ther 327:doi;10.1124/jpet.108.144, 2008). In conclusion, NS11394 has a unique subtype-selective GABA(A) receptor profile and represents an excellent pharmacological tool to further our understanding on the relative contributions of GABA(A) receptor subtypes in various therapeutic areas.

Strain- and model-dependent effects of chlordiazepoxide, L-838,417 and zolpidem on anxiety-like behaviours in laboratory mice.

The promise of subtype-selective GABA(A) receptor drugs with anxiolytic properties but with a much reduced side-effect burden (compared to benzodiazepines) is an attainable goal. However, its achievement necessitates the availability of in vivo preclinical assays capable of demonstrating differences as well as similarities between subtype-selective agents and non-selective benzodiazepines. In this study, we have compared three mouse strains (NMRI, C57BL/6J and DBA/2) in four models of anxiety-like behaviour (plus-maze, zero-maze, light-dark, and Vogel conflict). Furthermore, in each model, we have contrasted in detail the behavioural responses of each strain to the non-selective benzodiazepine chlordiazepoxide (CDP; 5-20 mg/kg), and the subtype-selective agents L-838,417 (GABA(A)-alpha(2/3/5); 3-30 mg/kg) and zolpidem (GABA(A)-alpha1; 0.3-3.0 mg/kg). The data show a complex mouse strainxmodelxpharmacological agent interaction. Most importantly, not all mouse strainxmodel test systems showed a positive response to CDP or predicted the response to L-838,417. This dissociation between CDP and L-838,417 opens up opportunities for preclinical test systems that differentiate subtype-selective and non-selective GABA(A) receptor agents, an attribute that might well be important in providing the necessary confidence for further drug development. Present findings suggest the need for a much greater focus on defining test systems appropriate for screening novel chemical entities, rather than self-selection of models or genotypes based on responses to known pharmacological agents. For example, if current data with L-838,417 are confirmed with compounds showing similar selectivity profiles, such agents may in future be best identified and characterised using test systems comprising NMRI mice in the zero-maze and/or C57 mice in the Vogel conflict and/or light-dark tests.

Merged imaging and expanded target selection in gamma knife radiosurgical ablation of the sphenopalatine ganglion.

Sphenopalatine neuralgia, or Sluder's neuralgia, refers to a consistent clustering of clinical symptoms: intermittent episodes of vasomotor hyperactivity causing conjuctival injection, lacrimation, serous nasal discharge and unilateral nasal mucosal inflammation, sensory disturbances of the palate and oropharynx with distorted gustatory sensations, and lancing, unilateral pain most often located in the area of the inferomedial orbit and nasal base or at the region of the mastoid process. This particular clinical entity has also proven difficult to manage effectively, especially when not clearly secondary to other medical conditions such as paranasal sinus infection or bony nasal deformities. This condition has been treated with success using Gamma Knife radiosurgery in at least 1 other case reported in the literature. We present a second patient whose sphenopalatine neuralgia was treated successfully with stereotactic radiosurgery and discuss the possibilities of this modality as an option for patients with a refractory condition.

Medialisation thyroplasty with tensor fascia lata: a novel approach for reducing post-thyroplasty complications.

BACKGROUND: Medialisation thyroplasty is considered the 'gold standard' treatment for unilateral vocal fold paralysis, enabling improvement of voice and swallowing function, and preventing life-threatening aspiration events. The most commonly used laryngeal implants induce some degree of local tissue inflammatory response, and carry the risk of immediate or delayed implant extrusion. METHODS: This paper describes a novel approach for medialisation thyroplasty. Specifically, it utilises a ribbon of autologous tensor fascia lata harvested at the time of surgery. This is layered within the paraglottic space in a manner similar to Gore-Tex thyroplasty. RESULTS: Thus far, this method has been accomplished in two patients with unilateral vocal fold paralysis, who also received prior radiotherapy to the head and neck. CONCLUSION: Given the increased risk of post-operative wound breakdown and infection in irradiated patients, it is suggested that this new approach will lead to improved outcomes, and a decrease in complications such as extrusion or wound infection, particularly in this patient population.

Proposed anti-HSV compounds isolated from Simira species.

Secondary metabolites isolated from Simira eleiezeriana and Simira glaziovii were evaluated against herpes simplex virus (HSV-1) and (HSV-2). The 50% effective concentrations values (EC50) were calculated from the dose-response curve and the selectivity index (SI) against the virus. The physicochemical data LogP, (PSA), (NRB), (HBA) and (HBD) were obtained using Marvin Sketch. Among the tested compounds, conipheraldeyde, harman and simirane A showed better results with EC50 6.39; 4.90; 4.61 µg/mL and SI 78.3; 11.8; 7.01, respectively, for HSV-1, and EC50 41.2; 71.8; 3.73 µg/mL and SI 12.1; 24.7; 8.7, respectively, for HSV-2. The percentage of inhibition (PI) obtained for HSV-1 were higher than 60%, and for HSV-2 these compounds showed PI > 90%. The physical chemical data showed that the most active compounds satisfy the attributes for drugs with good oral bioavailability.

Serotonin transporter density and anxiolytic-like effects of antidepressants in mice.

BACKGROUND: Chronic treatment with the dual serotonin/noradrenaline reuptake inhibitor (SNRI) duloxetine reduces the density of serotonin transporter sites in cortex and engenders an anxiolytic-like response. To determine the reproducibility of these effects and their generality to other antidepressants we compared the effects of chronic duloxetine treatment with another SNRI, venlafaxine, and two selective serotonin reuptake inhibitors, paroxetine and fluoxetine. METHODS: Separate groups of mice were administered vehicle, fluoxetine (15 mg/kg), paroxetine, duloxetine or venlafaxine (10 mg/kg) perorally twice daily for 28 days and tested in the mouse zero-maze and in motility cages on days 21 and 22, respectively, to determine effects on anxiety and motor activity. On day 28 brains were analysed for serotonin transporter (SERT) density in cortex and noradrenaline transporter (NET) density in cortex and hippocampus. RESULTS: Duloxetine and fluoxetine both reduced SERT density in cortex and induced anxiolytic-like effects. Paroxetine had an identical profile, but it is unclear if this drug down-regulated the SERT since extensive washing of cortical tissue did not remove all drug. Venlafaxine had no effect on behavioural or biochemical parameters. Only duloxetine reduced NET density in cortex, although not hippocampus. CONCLUSIONS: The reduction in SERT density and anxiolytic-like effects with duloxetine, fluoxetine and, potentially, paroxetine suggest that down-regulation of the SERT may be a relevant mechanism in therapeutic response to these antidepressants.

Predictive accuracy of standard computed tomography scanning in the diagnosis of Chiari malformation Type I in children.

OBJECT: In this study, retrospective data analysis was performed to analyze the utility of head computed tomography (CT) scanning in the diagnosis of Chiari malformation Type I (CM-I) in the pediatric population. METHODS: The authors conducted a retrospective review of radiology charts describing head CT results obtained at Columbus Children's Hospital between January 2004 and January 2005. The records were searched for the key words "Chiari," "cerebellar ectopy," or "tonsillar ectopy." The exclusion criteria included patients with previously known Chiari malformation Type I or Type II or those who had undergone follow-up magnetic resonance (MR) imaging at other institutions. Head CT and MR images for the remaining patients were reviewed to verify accuracy. RESULTS: Of the 72 patients with suspicious findings of tonsillar ectopy on CT, only 37 (51.4%) had MR imaging findings consistent with CM-I. The tonsillar ectopy in these patients ranged from 3 mm to 17 mm below the foramen magnum. CONCLUSIONS: The authors' findings indicate that incidental standard CT scans of the head have limited value in identifying CM-I.