Antidiabetic and haematological effect of aqueous extract of stem bark of Afzelia africana (Smith) on streptozotocin-induced diabetic Wistar rats

Objective

To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana (A. africana) and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.

Methods

A total of 30 rats including 24 diabetic and 6 normal rats were used for this study. Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin. After being confirmed diabetic, animals were orally treated with distilled water or extracts at 100 or 200 mg/kg body weight daily for 10 days. The haematological parameters including red blood and white blood cells and their functional indices were evaluated in diabetic treated groups compared with the controls.

Results

The extract significantly reduced the blood glucose levels while the best result was obtained at 200 mg/kg body weight. The feed and water intake in diabetic rats were significantly reduced while weight loss was minimized at both dosages. Similarly, the levels of red blood, white blood cells and their functional indices were significantly improved after extract administration at both doses.

Conclusions

It can be concluded that the aqueous extract of bark of A. africana possesses antihyperglycemic properties. In addition, the extract can prevent various complications of diabetes and improve some haematological parameters. Further experimental investigation is needed to exploit its relevant therapeutic effect to substantiate its ethnomedicinal usage.     

Tackling frontal lobe–related functions in PKU through functional brain imaging: a Stroop task in adult patients

Background  

Profound mental retardation in phenylketonuria (PKU) can be prevented by a low phenylalanine (Phe) diet. However, even patients treated early have inconsistently shown deficits in several frontal lobe–related neuropsychological tasks such as the widely accepted Stroop task. The goal of this study was to investigate whether adult patients exhibit altered brain activation in Stroop-related locations in comparison to healthy controls and if an acute increase in blood Phe levels in patients has an effect on activation patterns.     

Brain correlates of hypnotic paralysis-a resting-state fMRI study

Hypnotic paralysis has been used since the times of Charcot to study altered states of consciousness; however, the underlying neurobiological correlates are poorly understood. We investigated human brain function during hypnotic paralysis using resting-state functional magnetic resonance imaging (fMRI), focussing on two core regions of the default mode network and the representation of the paralysed hand in the primary motor cortex. Hypnotic suggestion induced an observable left-hand paralysis in 19 participants. Resting-state fMRI at 3T was performed in pseudo-randomised order awake and in the hypnotic condition. Functional connectivity analyses revealed increased connectivity of the precuneus with the right dorsolateral prefrontal cortex, angular gyrus, and a dorsal part of the precuneus. Functional connectivity of the medial frontal cortex and the primary motor cortex remained unchanged. Our results reveal that the precuneus plays a pivotal role during maintenance of an altered state of consciousness. The increased coupling of selective cortical areas with the precuneus supports the concept that hypnotic paralysis may be mediated by a modified representation of the self which impacts motor abilities.     

Lymphoma arising from Hashimoto's thyroiditis: an unusual cause of acute stridor

We report an unusual presentation of non-Hodgkin's lymphoma of the thyroid which mimicked an acute infective thyroiditis and was associated with acute stridor and dysphagia. The mode of presentation and diagnosis of thyroid lymphoma are discussed and the value of early fine needle aspiration emphasised.     

Cytokine and IDO metabolite changes effected by calcium pterin during inhibition of MDA-MB-231 xenograph tumors in nude mice

In vivo studies of the effectiveness of various forms of calcium pterin reveal significant antitumor activity associated with (1:4, mol/mol) calcium pterin (CaPterin), (1:2, mol/mol) calcium pterin, dipterinyl calcium pentahydrate (DCP), as well as unexpectedly for a calcium chloride dihydrate solution in nude mice with MDA-MB-231 xenographs. Stepwise regression analysis of nine plasma cytokine and indoleamine 2,3-dioxygenase (IDO) metabolite levels identified four effects correlated to (1:4, mol/mol) calcium pterin administration: (1) decreased IL-6, (2) increased IL-10, (3) decreased IFN-gamma, and (4) increased kynurenine. CONCLUSION: (1:4, mol/mol) CaPterin exerts significant (by Spearman rank order correlation) dose-response antitumor activity in nude mice with MDA-MB-231 xenographs, and sustains both inflammatory and anti-inflammatory changes in the levels of certain plasma factors.     

Upper gastrointestinal endoscopy findings in Mbale Regional Referral Hospital,Eastern Uganda: a 10-year retrospective analysis

BackgroundEndoscopy is required for formal diagnosis of many upper gastrointestinal (UGI) conditions including oesophageal cancer (OC). There is a paucity of data on endoscopy findings in East Africa as access to testing is challenging for patients. We describe the findings of 10 years of UGI endoscopy in Mbale Regional Referral Hospital (MRRH).MethodRecords of patients that underwent UGI endoscopy in MRRH, November 2009 – March 2019 were retrospectively analysed. Indication, macroscopic findings, histology and patient demographics were retrieved. Sub-group analyses were performed on those with a histological diagnosis of oesophageal cancer.Results833 eligible patients received single UGI procedures during the study period. Mean age was 54.8 years, range 16-93 years and 56.9% of patients were male. The main indication was dysphagia (42%) and the most common findings OC (34%) and gastritis (28%). 151 patients had histologically proven OC with a median age of 60 years and a 2:1 male to female ratio. 145/151 (96%) of samples tested revealed squamous cell carcinoma (SCC).ConclusionThose undergoing endoscopy in MRRH are most commonly male patients presenting in their 5th decade with dysphagia. There is a high proportion of significant findings including gastritis, peptic ulcer disease, and oesophageal cancer.     

Structural requirements for inhibition of the neuronal nitric oxide synthase (NOS-I): 3D-QSAR analysis of 4-oxo- and 4-amino-pteridine-based inhibitors

The family of homodimeric nitric oxide synthases (NOS I-III) catalyzes the generation of the cellular messenger nitric oxide (NO) by oxidation of the substrate L-arginine. The rational design of specific NOS inhibitors is of therapeutic interest in regulating pathological NO levels associated with sepsis, inflammatory, and neurodegenerative diseases. The cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H(4)Bip) maximally activates all NOSs and stabilizes enzyme quaternary structure by promoting and stabilizing dimerization. Here, we describe the synthesis and three-dimensional (3D) quantitative structure-activity relationship (QSAR) analysis of 65 novel 4-amino- and 4-oxo-pteridines (antipterins) as inhibitors targeting the H(4)Bip binding site of the neuronal NOS isoform (NOS-I). The experimental binding modes for two inhibitors complexed with the related endothelial NO synthase (NOS-III) reveal requirements of biological affinity and form the basis for ligand alignment. Different alignment rules were derived by building other compounds accordingly using manual superposition or a genetic algorithm for flexible superposition. Those alignments led to 3D-QSAR models (comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA)), which were validated using leave-one-out cross-validation, multiple analyses with two and five randomly chosen cross-validation groups, perturbation of biological activities by randomization or progressive scrambling, and external prediction. An iterative realignment procedure based on rigid field fit was used to improve the consistency of the resulting partial least squares models. This led to consistent and highly predictive 3D-QSAR models with good correlation coefficients for both CoMFA and CoMSIA, which correspond to experimentally determined NOS-II and -III H(4)Bip binding site topologies as well as to the NOS-I homology model binding site in terms of steric, electrostatic, and hydrophobic complementarity. These models provide clear guidelines and accurate activity predictions for novel NOS-I inhibitors.