Evaluation of the Toxicity and Reversibility Profile of the Aqueous Seed Extract of Hunteria Umbellata (K. Schum.) Hallier F. in Rodents

Hunteria umbellata (K. Schum.) Hallier f. (family: Apocynaceae) is reputed for the folkloric management of labour, pain and swellings, stomach ulcers, diabetes, obesity, and anaemia, with no scientific report of its toxicity and reversibility profile. The present study was, therefore, aimed at investigating the in vivo toxicity and reversibility profile of the aqueous seed extract of Hunteria umbellata (HU). The acute oral and intraperitoneal toxicity studies of HU were determined in Swiss albino mice while its 90-day oral toxicity and toxicity reversibility profile on anthropometric, biochemical, haematological and histopathological parameters were also assessed using standard procedures. Results showed that the LD₅₀ values for the acute oral and intraperitoneal toxicity studies for HU were estimated to be 1000 mg/kg and 459.3 mg/kg, respectively. Visible signs of immediate and delayed toxicities including starry hair coat, respiratory distress, and dyskinesia were observed. For the chronic oral toxicity study, HU administered for 90 days produced significant (p<0.001) reductions in the weight gain pattern and significant (p<0.001) and dose related increases in the relative weights of liver, stomach, spleen, testis, lungs and heart, at the 100 and 500 mg/kg of HU. Chronic HU treatment also produced significant (p<0.05, p<0.001) dose related reductions in the serum levels of fasting blood glucose, bicarbonate, urea and creatinine while causing non-significant (p>0.05) alterations in the serum levels of sodium, potassium, alaninine transaminase, aspartate transaminase, alkaline phosphatase, total and conjugated bilirubin, total protein and albumin. Also, chronic oral treatment with HU produced significant (p<0.05, p<0.01, p<0.001) and dose-related increases in the red cell count, packed cell volume, haemoglobin concentration, platelet count, total leucocyte count and lymphocyte differential while producing significant (p<0.05) reductions in neutrophil and granulocyte differentials. HU also produced histological features of proliferations of the stomach epithelia, lung tissues, splenic white and red pulps, and testicular spermatogenic series. Following 14 days of oral toxicity reversibility test, there was no significant (p>0.05) reversal in the serum levels of the biochemical and haematological parameters investigated, including the HU-induced histological lesions.Overall, results of this study showed that HU has a relatively low oral toxicity profile but its prolonged use, particularly, at high doses should be with great caution.Key words: Hunteria umbellata, Toxicity and reversibility profile, Haematology, Liver and Renal function tests, Histopathology, Rodents     

Hepatocellular carcinoma and the underlying mechanisms

The incidence of hepatocellular carcinoma is increasing worldwide as well as the associated risk factors, some of which include exposure to aflatoxin B1, Hepatitis B (HBV) virus and hepatitis C (HCV) virus. Mutation of tumour suppressor gene p53 at codon 249^ser at exon 7 has been found to contribute significantly to replication of damaged DNA and subsequent tumour progression. The x gene of HBV (HBx) is the most common open reading frame integrated into the host genome in hepatocellular carcinoma and the integrated HBx is frequently mutated in hepatocellular carcinoma. Mutant HBx proteins still retain their ability to bind to p53 thereby attenuating DNA repair and p53-mediated apoptosis.     

In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties

Background and purpose:

The histamine H₄ receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H₄ receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine).

Experimental approach:

We have analysed the pharmacological profile of A-940894 at mouse native, rat recombinant and human recombinant and native, histamine H₄ receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan-induced peritonitis.

Key results:

A-940894 potently binds to both human and rat histamine H₄ receptors and exhibits considerably lower affinity for the human histamine H₁, H₂ or H₃ receptors. It potently blocked histamine-evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine-induced shape change of mouse bone marrow-derived mast cells and chemotaxis of human eosinophils in vitro. In a mouse mast cell-dependent model of zymosan-induced peritonitis, A-940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D₂ levels. Finally, A-940894 has good pharmacokinetic properties, including half-life and oral bioavailability in rats and mice.

Conclusions and Implications:

These data suggest that A-940894 is a potent and selective histamine H₄ receptor antagonist with pharmacokinetic properties suitable for long-term in vivo testing and could serve as a useful tool for the further characterization of histamine H₄ receptor pharmacology.     

Plasma total homocysteine （THCY） level and other biochemical risk factors in hypertensives with and without cardiovascular events

Objective： The aim of this study is to assess the correlation between traditional cardiovascular risk factors and elevated plasma tHcy level in Nigerian hypertensive. Methods： Thirty-six hypertensive patients were recruited with 36 age and sex-matched controls. The age, sex and anthropometric measurements including height, weight and body mass index （BMI） were taken. Plasma total cholesterol, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, triglycerides and tHcy were analyzed. The results of the two groups were compared. Results： The mean total cholesterol and LDL- C were significantly higher in the subjects than in the controls （P = 0.01 and 0.03 respectively）. On the other hand, means of HDL-C and triglycerides were not significantly different between the two groups （P =0.06 and 0.68 respectively）. Mean total plasma tHcy was （ 12.95 ±4.9） μmol/L in hypertensive patients when compared with （ 11.29 ±3.6） μmol/L in the controls （P = 0.09） , however the mean tHcy was significantly higher in hypertensive patients who had stroke or myocardial infarction than those without these complications （one way Anova F = 3.63, P = 0.04）. Significant positive correlation was seen between tHcy and systolic blood pressure, diastolic blood pressure, BMI and LDL-C. Conclusion ： The study suggests that elevated plasma tHcy may predict occurrence of cardiovascular complications in hypertensive individuals.     

PLUNC protein expression in major salivary glands of HIV‐infected patients

Oral Diseases (2011) 17 , 258–264 Objective: To analyse and compare the expression of Palate, Lung, and Nasal Epithelium Clone (PLUNC) proteins in salivary glands from patients with and without AIDS (control group) using autopsy material. Methods: We analysed the expression of PLUNCs using immunohistochemistry in parotid (n = 45), submandibular (n = 47) and sublingual gland (n = 37) samples of AIDS patients [30 with normal histology, 21 with mycobacteriosis, 14 with cytomegalovirus (CMV) infection, 30 with chronic non‐specific sialadenitis, and 30 HIV‐negative controls. In situ hybridization (ISH) for SPLUNC 2 in the HIV‐negative group was performed. Results: SPLUNC 1 expression was detected in the mucous acini of submandibular and sublingual glands, and SPLUNC 2 were seen in the serous cells. LPLUNC 1 expression was only positive in the salivary ducts. There was a higher expression of SPLUNC 2 in AIDS patients with CMV infection and mycobacteriosis when compared with all other groups. The intensity of staining for SPLUNC 2 was greater around the lesions than the peripheral ones. ISH for SPLUNC 2 showed perinuclear positivity in the serous cells in all HIV‐negative cases. Conclusions: SPLUNC 1 and LPLUNC 1 proteins were similarly expressed in the salivary glands of AIDS patients and non‐HIV patients. CMV infection and mycobacteriosis increase SPLUNC 2 expression in serous cells in the salivary gland of AIDS patients.     

Follow-up of newborns treated with extracorporeal membrane oxygenation: a nationwide evaluation at 5 years of age

Introduction  

Extracorporeal membrane oxygenation (ECMO) is a supportive cardiopulmonary bypass technique for babies with acute reversible cardiorespiratory failure. We assessed morbidity in ECMO survivors at the age of five years, when they start primary school and major decisions for their school careers must be made.     

Longitudinal correlates of the persistence of irregular eating from age 5 to 14 years

Aim:  To report the stability of parent-perceived child irregular eating from 6 months to 14 years of age and to investigate a predictive model inclusive of child and parent factors.
Methods:  Of the 7223 singleton children in a birth cohort, 5122 children were re-interviewed at 5 years and 4554 for the 14-year analysis. Information was obtained from structured interviews including questions answered by parents of the child at birth, 6 months, 5 years and 14 years; and by teenagers at age 14 years and from physical measures of the child. The mother's perception that the child was an irregular eater at age 14 years was the major outcome variable of interest.
Results:  Approximately 40% of irregular eaters at age 5 will still be irregular eaters at age 14 years. This was not related to maternal education or socio-economic class. Significant at multivariate analysis were infant feeding problems and the children's ability to regulate their sleep and mood. Significant maternal factors were greater age, not feeling positive about the baby and persistent maternal anxiety during the child's early years.
Conclusion:  Irregular eating behaviour displays considerable continuity from childhood to mid-adolescence. Independent contributions to this behavioural phenotype include child biological and psychological factors and maternal anxiety during the child's early years.