At-Home Administration of Gantenerumab by Care Partners to People with Early Alzheimer's Disease: Feasibility, Safety and Pharmacodynamic Impact.

BACKGROUND: Monoclonal antibodies that target amyloid-beta and remove amyloid plaques can slow cognitive and functional decline in early Alzheimer's disease. Gantenerumab is a subcutaneously administered fully-human anti-amyloid-beta monoclonal antibody with highest affinity for aggregated amyloid-beta. Since the phase 3 GRADUATE trials did not meet the primary endpoint (change from baseline to Week 116 in Clinical Dementia Rating scale - Sum of Boxes), development of gantenerumab in sporadic Alzheimer's disease was stopped and all ongoing trials were terminated early due to sponsor decision. Subcutaneous administration at the clinic or at home by care partner would be an important option for other therapies in this class in order to increase flexibility and reduce overall burden. The insights obtained from the experience with gantenerumab home administration by care partner in the phase 2 GRADUATION trial will serve to guide the ongoing efforts with other anti-amyloid-beta antibodies. OBJECTIVES: To evaluate the pharmacodynamic effects on brain amyloid load of once weekly subcutaneous administration of gantenerumab and the safety and feasibility of home administration by care partners. DESIGN: Phase 2, open-label, single arm study. SETTING: Multicenter trial conducted in 33 sites in 8 countries from November 2020 to March 2023. PARTICIPANTS: Participants aged 50 to 90 with early symptomatic Alzheimer's disease (mild cognitive impairment/mild dementia due to Alzheimer's disease), and evidence of amyloid positron emission tomography positivity. INTERVENTION: Participants could receive up to 255 mg gantenerumab once-weekly, administered subcutaneously at site or at home by healthcare professionals or non-healthcare-professional care partners. MEASUREMENTS: The primary endpoint was the change from baseline to Week 52 and to Week 104 in brain amyloid load as measured by PET centiloid levels. The secondary endpoints were responses to the home administration questionnaire, plasma concentrations and safety. RESULTS: The overall number of participants enrolled was 192, with a mean (standard deviation) amyloid PET load at baseline of 101.80 (29.80) centiloids. At the time of early study termination by sponsor, 149 participants had valid Week 52 amyloid PET data (primary endpoint), and 12 participants had an early termination PET within the pre-defined time range of Week 104. The mean change in amyloid PET from baseline to Week 52 and Week 104 was -26.19 centiloids (range: -75.6-15.8; n=149) and -35.48 centiloids (range: -63.2--7.0; n=12), respectively. Responses to the home administration questionnaire at Week 52 (n=148) indicated that the majority of care partners (88-97%) considered administration of study drug at home easy (30.4%) or very easy (57.4%), and convenient (25.7%) or very convenient (70.9%). Care partners felt confident (31.1%) or very confident (62.2%) and satisfied (29.7%) or very satisfied (64.9%) with giving the injection at home. Responses by care partners at Week 36 (n=72), Week 76 (n=126) and Week 104 (n=29) and participant (patient) assessment of convenience and satisfaction at these time points were similar. There were no new safety findings associated with gantenerumab administered subcutaneously once weekly at 255 mg or safety issues associated with at-home injections by non-healthcare professional care partners. CONCLUSIONS: Once-weekly subcutaneous home administration of the anti-amyloid-beta antibody gantenerumab by non-healthcare-professional care partners to participants with early Alzheimer's disease was feasible, safe, well tolerated, and considered as a convenient option by both the care partners and participants with Alzheimer's disease. Although gantenerumab's development has been stopped due to lack of efficacy, this approach has the potential to reduce the frequency of hospital/outpatient clinic visits required for treatment with other anti-amyloid-ß antibodies and can increase flexibility of drug administration for people living with Alzheimer's disease and their families.

Brain antioxidant status and gene expressions of nicotinic and dopamine receptors are improved by black seed oil administration in cigarette smoke or nicotine vapour-exposed rats.

BACKGROUND: Smoking is associated with dysregulation of the antioxidant system and addiction. AIM: This study sought to ascertain the effect of Nigella Sativa (NS) oil on the antioxidant system, nicotine/tobacco addiction as well as the expressions of α4ß2 nicotinic (nAChR) and dopamine type-2 (DRD2) receptors in selected brain regions of the rat. METHODS: Thirty male Sprague-Dawley rats were divided into 6 groups comprising of vehicle-treated control, NS oil only, Smoke only, Smoke + NS oil, Nicotine only and Nicotine + NS oil. Animals were passively exposed to cigarette smoke or nicotine vapour for 12 weeks, however, NS oil treatment commenced from 9th-12th week of the experimental duration. RESULTS: Nicotine vapour and cigarette smoke-induced increase in cotinine level were significantly ameliorated by NS treatment. Cigarette smoke or nicotine vapour exposure significantly (p<0.05) decreased the level of antioxidant enzymes while increasing malondialdehyde level in the brain homogenates of the rats.  Administration of NS oil significantly (p<0.05) reversed the reduced antioxidant level. Cigarette-smoke also significantly increased α4-nAChR expression in the frontal cortex and olfactory bulb compared to control. Nicotine vapour significantly increased DRD2 expression only in the olfactory cortex. NS oil administration reduced both the cigarette-smoke-induced increase in α4-nAChR and nicotine vapour-induced increase in DRD2 gene expression only in the olfactory cortex. CONCLUSION: Findings from this study suggest that NS oil improves brain antioxidant status while ameliorating nicotine vapour and cigarette smoke addiction through down-regulation of α4-nAChR and DRD2 gene expressions in discrete brain regions in Sprague-Dawley rats.

Prenatal urban traffic noise exposure impairs spatial learning and memory and reduces glucocorticoid receptor expression in the hippocampus of male rat offspring.

INTRODUCTION: Exposure to noise stress during early life may permanently affect the structure and function of the central nervous system. The aim of this study was to evaluate the effects of prenatal exposure to urban traffic noise on the spatial learning and memory of the rats' offspring and the expression of glucocorticoid receptors (GRs) in their hippocampi. METHODS: Three g\roups of pregnant rats were exposed to recorded urban traffic noise for 1, 2 or 4 h/day during the last week of pregnancy. At the age of 45 days, their male offspring were introduced to the Morris water maze (MWM) for assessment of spatial learning and memory. The corticosterone levels were measured in the offspring's sera by radioimmunoassay, and the relative expression of glucocorticoid and mineralocorticoid receptors (MRs) in their hippocampi was evaluated via RT-PCR. RESULTS: Facing urban traffic noise for 2 and 4 h/day during the third trimester of pregnancy caused the offspring to spend more time and to travel a larger distance than the controls to find the target platform. Analogously, these two groups were inferior to their control counterparts in the probe test. Also, prenatal noise stress elevated the corticosterone concentration in the sera of the rats' offspring and dose-dependently decreased the relative expression of the mRNA of both GRs and MRs in their hippocampi. CONCLUSIONS: Urban traffic noise exposure during the last trimester of pregnancy impairs spatial learning and memory of rat offspring and reduces GRs and MRs gene expression in the hippocampus.

Adapted MMSE and TYM cognitive tests: how much powerful in screening for Alzheimer's disease in Iranian people.

Alzheimer's disease (AD) is a major global health priority and providing an efficient way for early diagnosis of people developing dementia is important. The Mini-Mental State Examination (MMSE, total score = 30) and Test Your Memory (TYM, total score = 50) are widely used as screening tests for cognitive function. In the present study 174 subjects including healthy people (CON group) and those having Alzheimer's disease (AD group) were introduced to MMSE and TYM cognitive tests adjusted to Iranian population. Sensitivities and specificities with optimal cut-off scores, area under curve (AUC), positive predictive value (PPV) and negative predictive value (NPV) were measured for both tests. The MMSE scores of the CON and AD groups were 23.77 ± 0.327 and 10.88 ± 0.762, respectively. The TYM scores were 44.32 ± 0.389 and 14.37 ± 1.368 in the CON and AD participants, respectively. Findings in the MMSE test were: AUC = 0.962, optimal cut-off score = 18.5, sensitivity = 0.90 and specificity = 0.96. Values in the TYM test were: AUC = 0.991, optimal cut-off score = 31, sensitivity = 0.90 and specificity = 1. We found no correlation between the cognitive performance and age in the CON group but a positive correlation in the AD patients. On the other hand, t-test analysis indicated that achievement of the test scores are significantly sex dependent, with more scores attained by the females. Taken together, in regard to correct classification rate (CCR); the TYM test seems to be more appropriate for cognitive screening in our study. However, considering an analogous AUC, both tests are comparable and have high sensitivity and specificity for discriminating between people with and without AD.

Postnatal development and sensory experience synergistically underlie the excitatory/inhibitory features of hippocampal neural circuits: Glutamatergic and GABAergic neurotransmission.

During a postnatal critical period balance of excitation/inhibition in the developing brain is highly regulated by environmental signals. Compared to the visual cortex, rare document includes effects of sensory experience on the hippocampus, which is also bombarded by sensory signals. In this study, basic and tetanized field excitatory postsynaptic potentials (fEPSPs) were recorded in CA1 area of hippocampus of light-(LR) and dark-reared (DR) rats (at 2, 4 and 6weeks of age). Also, we assessed age- and activity-dependent changes in the N-Methyl-d-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors subunit compositions and, GABA producing enzymes. While the sensory deprivation increased amplitude of baseline fEPSPs, it decreased degree of potentiation of post-tetanus responses. Expression of GluA1 and GluA2 subunits of AMPA receptors was increased across age in DR rats. In contrast to LR rats, mRNA and protein expression of GluN1, GluN2A and GluN2B subunits of NMDA receptors was decreased in DR ones. Also, dark rearing diminished expression of GABA synthesis enzymes GAD65 and GAD67. These results indicate that, sensory experience adjusts synaptic plasticity and might also affect the balance of excitation/inhibition in the hippocampus.

Autolysis control and structural changes of purified ficin from Iranian fig latex with synthetic inhibitors.

The fig's ficin is a cysteine endoproteolytic enzyme, which plays fundamental roles in many plant physiological processes, and has many applications in different industries such as pharmaceutical and food. In this work, we report the inhibition and activation of autolysis and structural changes associated with reaction of ficin with iodoacetamide and tetrathionate using high-performance liquid chromatography (HPLC), ultra filtration membrane, and dynamic light scattering (DLS) methods. The ficin structural changes were also determined using UV-absorption, circular dichroism (CD), fluorescence spectroscopy, and differential scanning calorimetry (DSC) techniques. These techniques demonstrated that iodoacetamide completely inhibited ficin autolysis, which was irreversible. However, tetrathionate partially and reversibility inhibited its autolysis. The ficin structural changes with two synthetic inhibitors were associated with secondary structural changes related to decreased alpha-helix and increased beta sheet and random coil conformations, contributing to its aggregation.

EXPERIENCE WITH MANAGING RETROSTERNAL GOITRES IN IBADAN, NIGERIA.

BACKGROUND: There is no general consensus on the definition of retrosternal goitre (RSG) however thyroidectomy remains the gold standard of treatment with or without a sternotomy. AIM: To review the outcome of surgical management of retrosternal goitres. METHODOLOGY: Retrospective review of records of patients who had thyroidectomy for RSG over a 15-year period. RESULTS: Out of a total of 45 patients, 34(76%) were females and 11(24%) were males with a male/female ratio of 3:1; while their age ranged between 28 and 72years with a mean of 57+15SD. All the patients were euthyroid and a quarter did not have symptoms apart from a neck mass. In all, 15% of the patients had recurrent goitre. CT scan of neck and chest was done in 31 (72%) patients; while 44 (98%) patients had cervical retrosternal goitres, 1(2%) patient had ectopic retrosternal goitre. A cervical incision was sufficient in 28 (62%) patients while 17 (38%) patients required additional sternotomy. Total thyroidectomy was done in all the patients. There were post-operative complications in 19 (42%) patients. Histopathology showed that 3(6.6%) patients had papillary thyroid carcinoma while 42(93.4%) had benign pathology findings. CONCLUSION: Surgical removal is the treatment of choice. Most retrosternal goitres can be resected through a collar stud incision; however the possibility of a need for a sternotomy should always be planned. The simultaneous occurrence of cervical and ectopic retrosternal goitre should always be ruled out with a CT scan.

Surgical management of giant lumbar disc herniation: analysis of 154 patients over a decade.

BACKGROUND: We describe a decade of our experience in the surgical management of patients with giant lumbar intervertebral disc herniation (GILID). METHODS: This is a case series of patients operated for a GILID between 2000 and 2009. Among 1334 patients eligible for the present study: 154 patients presented with GILID (study group) and 1180 patients without GILID (control group). Clinical symptoms and preoperative imaging results were obtained from medical records. Complications and long-term results were assessed. RESULTS: This retrospective study documents the characteristic features between patients with and without GILID. The difference in the incidence of female patients was statistically significant between the study group and the control group as was the mean duration of symptoms, hyperalgic radicular pain, bilaterality of symptoms, preoperative motor deficit, central location of lumbar disc herniation (LDH), contained herniation and recurrence of LDH. CONCLUSIONS: GILIDs are a distinct entity: they are distinctly uncommon compared with smaller herniations, patients were statistically more likely to be hyperalgic with bilateral radicular pain and often associated with neurological deficits. The majority of patients do not display a cauda equina syndrome (CES). Low lumbar disc sites are mostly affected and disc fragments are more likely to be central-uncontained. The recurrence rate is lower for GILIDs.

A Real Valued Neural Network Based Autoregressive Energy Detector for Cognitive Radio Application.

A real valued neural network (RVNN) based energy detector (ED) is proposed and analyzed for cognitive radio (CR) application. This was developed using a known two-layered RVNN model to estimate the model coefficients of an autoregressive (AR) system. By using appropriate modules and a well-designed detector, the power spectral density (PSD) of the AR system transfer function was estimated and subsequent receiver operating characteristic (ROC) curves of the detector generated and analyzed. A high detection performance with low false alarm rate was observed for varying signal to noise ratio (SNR), sample number, and model order conditions. The proposed RVNN based ED was then compared to the simple periodogram (SP), Welch periodogram (WP), multitaper (MT), Yule-Walker (YW), Burg (BG), and covariance (CV) based ED techniques. The proposed detector showed better performance than the SP, WP, and MT while providing better false alarm performance than the YW, BG, and CV. Data provided here support the effectiveness of the proposed RVNN based ED for CR application.

Antioxidative responses in calli of two populations of Acanthophyllum laxiusculum with and without B-chromosomes under salt stress.

Salinity is one of the most significant stresses that affect plant growth and agricultural production. Considerable efforts have therefore been made to investigate how plants respond to salt stress. To investigate the responses of Acanthophyllum to salinity stress, changes on lipid peroxidation, H2O2 content and the activity of antioxidant enzymes in calli of two Acanthophyllum laxiusculum variants, without (variant A) and with (variant B) B-chromosomes, were analyzed. Under salinity stress, lipid peroxidation and H2O2 content decreased in variant A compared to variant B. Moreover, variant A produced a higher amount of proline under salt stress than variant B. In calli of variant A, salinity stress preferentially enhanced the activities of the superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), ascorbate peroxidase (APX, EC 1.11.1.11) and glutathione reductase (GR, EC 1.6.4.2), whereas it decreased their activity in variant B. Guaiacol peroxidase (GPX, EC 1.11.1.7) activity decreased with increasing NaCl concentrations in variant A but its activity increased in variant B. After native polyacrylamide gel electrophoresis (PAGE) analysis, calli of both A and B variants had only Mn-SOD and Fe-SOD isoforms. Expression of the isoforms mentioned above, showed marked increase in variant A; while in variant B salinity caused a significant reduction as compared to control. Moreover, changes in the CAT and GPX isoforms pattern of treated plants were in accordance with the activity changes in time. These results suggest that variant A was able to induce better antioxidative responses against salt stress than variant B.

Robust classification of motor imagery EEG signals using statistical time-domain features.

The tradeoff between computational complexity and speed, in addition to growing demands for real-time BMI (brain-machine interface) systems, expose the necessity of applying methods with least possible complexity. Willison amplitude (WAMP) and slope sign change (SSC) are two promising time-domain features only if the right threshold value is defined for them. To overcome the drawback of going through trial and error for the determination of a suitable threshold value, modified WAMP and modified SSC are proposed in this paper. Besides, a comprehensive assessment of statistical time-domain features in which their effectiveness is evaluated with a support vector machine (SVM) is presented. To ensure the accuracy of the results obtained by the SVM, the performance of each feature is reassessed with supervised fuzzy C-means. The general assessment shows that every subject had at least one of his performances near or greater than 80%. The obtained results prove that for BMI applications, in which a few errors can be tolerated, these combinations of feature-classifier are suitable. Moreover, features that could perform satisfactorily were selected for feature combination. Combinations of the selected features are evaluated with the SVM, and they could significantly improve the results, in some cases, up to full accuracy.

Potassium sorbate as an AGE activator for human serum albumin in the presence and absence of glucose.

Advanced glycation end products (AGEs) are the predominant intermediates of glycation process, and mediate oxidative stress and complications of diabetes. Potassium sorbate (PS) as a widespread preservative is an oxidative agent and used in different dairy and drug products, which can readily enter biological matrices. Here we studied the PS interference with glycation of human serum albumin (HSA) in the presence of glucose (Glc) using various techniques. These included TNBSA assay, circular dichroism, fluorescence spectroscopy, differential scanning calorimetry (DSC), Th T assay, and atomic force microscopy. Our results indicated that HSA glycation was accelerated in the presence of PS. Furthermore, PS produced AGEs in the absence of glucose. Secondary and tertiary structural changes were also observed in HSA incubated with glucose in the presence or absence of PS through beta-sheet inducing effects. Th T assay demonstrated the role of PS in HSA fibril formation in the presence or absence of glucose. Atomic force microscopy determined different amyloid fibril formation in HSA incubated with PS in the presence or absence of glucose. Together our results indicated that PS has a stimulatory effect on glycation and fibrillation of HSA in the presence or absence of glucose, and could exacerbate complication of diabetes.

Thermal inactivation and conformational lock studies on horse liver alcohol dehydrogenase: structural mechanism.

Horse liver alcohol dehydrogenase (HLADH) is a two subunits metal enzyme that has two catalytic sites and two coenzyme domains for each subunit. These subunits are connected together by coenzyme domains. In this study, we investigated the number and sequences of residues that participated in interface locks of HLADH. For this purpose, the kinetics of thermal inactivation of HLADH were studied in a 50 mM pyrophosphate buffer, pH 8.8, using ethanol as a substrate and NAD(+) as a cofactor. The temperature range was between 46°C and 55°C and the conformational lock was developed based on the Poltorak theory and analysis of the curves was done by the conformational lock method for oligomeric enzymes. The conformational lock number of HLADH was 2 when calculated experimentally. The results were confirmed by the Ligplot program computations. Using computational method it was shown that there are two patches binding sites at the interface and they spread over two regions of each chain. In this study we also proposed a thermal denaturation mechanism for HLADH by using different techniques such as UV-Vis fluorescence and circular dichroism (CD) spectroscopy and dynamic light scattering (DLS). The subunits are dissociated and several intermediates appeared during inactivation through increasing the temperature. DLS measurement was performed to study the changes in hydrodynamic radius during thermal inactivation. The three distinct zones that were shown by DLS were also confirmed by fluorescence and CD techniques.

Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis.

Diabetes mellitus-induced metabolic disturbances underlie the action of many systems including some higher functions of the brain such as learning and memory. Plenty of evidence supports the effects of probiotics on the function of many systems including the nervous system. Here we report the effect of probiotics treatment on the behavioral and electrophysiological aspects of learning and memory disorders. Diabetic rats were made through intraperitoneal injection of streptozocin. The control and diabetic rats were fed with either normal regimen (control rats recieving normal regimen (CO) and diabetics rats receiving normal regimen (DC), respectively) or normal regimen plus probiotic supplementation for 2months (control rats receiving probiotic supplementation (CP) and diabetics rats recieving probiotic supplementation (DP), respectively). The animals were first introduced to spatial learning task in the Morris water maze. Then, in electrophysiological experiments, stimulating the Schaffer collaterals the basic and potentiated excitatory postsynaptic potential (EPSPs) were recorded in the CA1 area of the hippocampus. Finally, the serum levels of glucose, insulin, superoxide dismutase and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. We found that probiotics administration considerably improved the impaired spatial memory in the diabetic animals. The probiotics supplementation in the diabetic rats recovered the declined basic synaptic transmission and further restored the hippocampal long-term potentiation (LTP). While the probiotics administration enhanced the activation of superoxide dismutase and increased the insulin level of serum it decreased both the glucose level of serum and the 8-OHdG factor. From the present results we concluded that probiotics efficiently reverse deteriorated brain functions in the levels of cognitive performances and their proposed synaptic mechanisms in diabetes mellitus. These considerations imply on the necessity of an optimal function of the microbiome-gut-brain axis in the behavioral as well as electrophysiological aspects of brain action.

Comparison between NSAID and intra-articular corticosteroid injection in frozen shoulder of diabetic patients; a randomized clinical trial.

INTRODUCTION: Frozen shoulder or adhesive capsulitis is a relatively common encountered musculo-skeletal disease in which arouses following soft tissue involvement of glenohumeral joint and presents with pain and limitation of shoulder' active and passive motions. The incidence of frozen shoulder among diabetic patients is about 10-20%, stiffness in such patients is more severe and should be managed actively. Local Glucocorticoid injection, NSAIDs and physiotherapy each can relief the symptoms. The aim of this study was to compare the efficacy of glenohumeral injection of Glucocorticoid with NSAIDs in frozen shoulder of diabetic patients. METHOD: The randomized clinical trial study conducted during Feb 2009-Aug 2010 on diabetic patients with frozen shoulder that were referred to rheumatology and endocrinology clinics, Yazd, Iran. Diagnostic criteria of capsulitis were pain of shoulder and range of motion limitation in all directions. The patients were divided into 2 groups, patients of first group received NSAID while the latter group were undergone intra-articular corticosteroid injection. After 1 week, home exercise was done for both group and evaluation of the patients after first visit was done likewise 2nd, 6th, 12th and 24th weeks. All registered data were transformed into SPSS-15 software and analyzed. RESULTS: Totally 57 patients (19 males (33.3%) and 38 females (66.7%) were included in the analysis. There was no significant difference between sex (P=0.4) and age (P=0.19) of patients. No significant relation was detected between 2 groups after 24 weeks according to range of motion in flexion (P=0.51), abduction (P=0.76), external rotation (0.12) and internal rotation (P=0.91). Also any significant difference in pain score was not detected (P=0.91). CONCLUSION: Based on our study, both intra-articular corticosteroid and NSAID are effective in treatment of adhesive capsulitis and there is no significant difference between efficacies of these 2 treatment modalities in diabetic patients.

CIVILIAN VASCULAR INJURIES IN AN URBAN AFRICAN REFERRAL INSTITUTION.

OJECTIVE: To evaluate the pattern of civilian vascular injuries, demonstrate any change in pattern and document management challenges in a resource challenged environment. DESIGN: A retrospective study. SETTING: The division of Thoracic and Cardiovascular Surgery of University College Hospital a major referral centre, not only for south-west Nigeria but for the whole country. SUBJECTS: All patients presenting with vascular injury through the division during the study period were recruited. There were no exclusion criteria. RESULTS: Males accounted for 85% of the study group. Mean age was 31.98 years (± 14.94 S.D.) with peak in 20-29 years group (28.3%). Stab and gunshot injury were responsible in 36.7% and 30% respectively. Upper limb vessels were involved in 58.3%. Delayed presentation (> 4 hrs postinjury) occurred in 58.3% and presentation-operation interval was four to six hours in 55% of cases. Specific diagnostic investigation was required in only 20%. Morbidity, amputation and mortality rates were 10.1, 3 and 6.7% respectively. CONCLUSION: Penetrating vascular injuries are on the increase amongst civilian population. Poor transportation and lack of organised referral system contribute to delay in surgical intervention. Prompt evaluation for hard signs of vascular injury is of immense value in deciding for surgery in our environment where patients have financial challenges and resources are limited.

Synergic study of α-glucosidase inhibitory action of aloin and its antioxidant activity with and without camel ß-casein and its peptides.

Regular consumption of natural antioxidants reduces the risk of developing diseases. Aloin is one of the main active phenolic components of Aloe vera. The main disadvantage of aloin is its concentration limit of use that causes cell damage. One of the aims of this study was to investigate the antioxidant activity of aloin in the presence and absence of camel ß-casein ( ß-CN) and its peptide fractions. The mixture of aloin, ß-CN and peptides showed a very high antioxidant activity in a synergistic manner as compared to each component alone. The alpha ( α)-glucosidase inhibitory activity of aloin was also investigated in the presence and absence of ß-CN and its peptides. Aloin alone is a potent inhibitor of α-glucosidase. The α-glucosidase inhibitory activity of aloin is reduced in the presence of ß-CN or its peptides. The combination of aloin and ß-CN or its peptides makes a high antioxidant functional ingredient.

Presentation pattern and management of effusive-constrictive pericarditis in Ibadan.

BACKGROUND: Effusive-constrictive pericarditis is a syndrome in which constriction by the visceral pericardium occurs in the presence of a dense effusion in a free pericardial space. Treatment of this disease is problematic because pericardiocentesis does not relieve the impaired filling of the heart and surgical removal of the visceral pericardium is challenging. We sought to provide further information by addressing the evolution and clinico-pathological pattern, and optimal surgical management of this disease. METHODS: We conducted a prospective review of a consecutive series of five patients managed in the cardiothoracic surgery unit of University College Hospital, Ibadan, in the previous year, along with a general overview of other cases managed over a seven-year period. This was followed by an extensive literature review with a special focus on Africa. RESULTS: The diagnosis of effusive-constrictive pericarditis was established on the basis of clinical findings of features of pericardial disease with evidence of pericardial effusion, and echocardiographic finding of constrictive physiology with or without radiological evidence of pericardial calcification. A review of our surgical records over the previous seven years revealed a prevalence of 13% among patients with pericardial disease of any type (11/86), 22% of patients presenting with effusive pericardial disease (11/50) and 35% who had had pericardiectomy for constrictive pericarditis (11/31). All five cases in this series were confirmed by a clinical scenario of non-resolving cardiac impairment despite adequate open pericardial drainage. They all improved following pericardiectomy. CONCLUSION: Effusive-constrictive pericarditis as a subset of pericardial disease deserves closer study and individualisation of treatment. Evaluating patients suspected of having the disease affords clinicians the opportunity to integrate clinical features and non-invasive investigations with or without findings at pericardiostomy, to derive a management plan tailored to each patient. The limited number of patients in this series called for caution in generalisation. Hence our aim was to increase the sensitivity of others to issues raised and help spur on further collaborative studies to lay down guidelines with an African perspective.

Effects of a single post-partum injection of a high dose of vitamin D on glucose tolerance and insulin resistance in mothers with first-time gestational diabetes mellitus.

AIM: This study was performed to determine the effect of a single, large, intramuscular injection of vitamin D post-partum on glucose tolerance and insulin resistance in women with gestational diabetes. METHODS: Forty-five participants in a randomized controlled trial on gestational diabetes mellitus were divided into an intervention group and a control group. Only subjects in the intervention group received one intramuscular injection of 300,000 IU of vitamin D3. HbA(1c), serum 25-hydroxyvitamin D3, fasting insulin and blood glucose, C-peptide, homeostasis model assessment insulin resistance index (HOMA-IR), ß-cell function, insulin sensitivity and the Quantitative Insulin Sensitivity Check Index (QUICKI) were measured at baseline and after 3 months of intervention. RESULTS: Approximately 80% of the mothers had a degree of vitamin D deficiency. Post-intervention, this was found in 4.2 and 71.4% in the intervention and control groups, respectively. The medians of HOMA-IR indices before and after intervention were 0.6 and 0.5 (P = 0.7), respectively, in subjects in the intervention group, and 0.5 and 0.9 (P = 0.01) in subjects in the control group. The mean of the QUICKI fell only in the control group (P = 0.008). In the control group, ß-cell function increased by ~8% (P = 0.01) and insulin sensitivity decreased after 3 months (P = 0.002). Post-intervention, the median C-peptide decreased in the intervention group and increased in the control group, but the change was significant only in the control group (P = 0.03). CONCLUSIONS: A single injection of 300,000 IU of vitamin D3 achieves a 3-month serum 25-hydroxyvitamin D range of 50-80 nmol/l and is an efficient, effective and safe procedure for improving the vitamin status and indices of insulin resistance in mothers with gestational diabetes after delivery.

Vascular intersection detection in retina fundus images using a new hybrid approach.

The use of vascular intersection aberration as one of the signs when monitoring and diagnosing diabetic retinopathy from retina fundus images (FIs) has been widely reported in the literature. In this paper, a new hybrid approach called the combined cross-point number (CCN) method able to detect the vascular bifurcation and intersection points in FIs is proposed. The CCN method makes use of two vascular intersection detection techniques, namely the modified cross-point number (MCN) method and the simple cross-point number (SCN) method. Our proposed approach was tested on images obtained from two different and publicly available fundus image databases. The results show a very high precision, accuracy, sensitivity and low false rate in detecting both bifurcation and crossover points compared with both the MCN and the SCN methods.