Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats

Copper deficiency inactivates Cu/Zn-SOD and promotes accumulation of reactive oxygen species. This process likely impairs nitric oxide (NO)-mediated relaxation as well as triggers vascular inflammation. The current study was designed to determine whether COX-2, a proinflammatory protein, expression and activity are upregulated in the oxidative environment associated with inadequate Cu. Weanling male Sprague Dawley rats were fed purified diets which were either Cu-adequate (Cu-A); Cu-marginal (Cu-M), Cu-deficient (Cu-D), or the Cu-D diet combined with the SOD mimetic Tempol (Cu-D/T; 1 mM in drinking water) for 4 weeks. COX-2 protein, PGE₂ (COX-2 metabolite) and isoprostanes (index of oxidative stress) were all higher in the Cu-D group vs Cu-A group, but no significant differences occurred between the Cu-M and Cu-A groups. Tempol protected against an attenuation of NO-mediated vasodilation in the Cu-D rats but did not prevent the elevation of PGE₂ or isoprostanes. Our data suggest a role for copper as a modulator of oxidative stress and inflammation independent of SOD activity or NO-derived oxidants.     

Vernal keratoconjunctivitis and intestinal parasitic infestations in black children

The study aimed at finding out any association between vernal keratoconjunctivitis (VKC) and intestinal worm infestations in black children in Nigeria. This is a report of a case-control study of a total of 117 cases of VKC and 198 controls, who were newly presenting to two hospitals in Ibadan. The controls were comparable to the cases in many respects. While 67 (57%) of cases admitted to previous passage of worms, 59 (50.5%) children actually had parasitic infestations. Of these 59 children, 30 (51%) were due to roundworm, 12 (20%) to hookworm, 14 (24%) to protozoal infestation and others, e.g., tapeworms, 13 (5%). Among controls, 36.8% had parasitic infestation, out of which roundworms were responsible for 11.6%, hookworms 7.6%, protozoa 14.1% and others 3.5%. Children with VKC have almost twice (odds ratio = 1.68) the risk of having been infested by worms. Both older age in children and roundworm infestation were not independent risk factors for VKC. There was no significant association among all ages, sex, hookworm and other worms with VKC. Deworming may prove beneficial for children with VKC; however, more studies with appropriate design are required to prove this.     

Retinoblastoma presenting with a cheek mass

This is a report of a case of retinoblastoma that mimicked Burkitt's lymphoma by presenting with a left proptosis and a right cheek mass. With the aid of fine-needle aspiration cytology, the diagnosis was established as retinoblasstoma and a left modified exenteration was performed. The patient had adjuvant chemotherapy and radiotherapy to the left orbit and the right maxilla with regression. At 12 months postoperatively, there was no evidence of recurrence, and the patient was still hale and hearty. In conclusion, this patient had left retinoblastoma with metastasis to the contralateral jaw. It is important to note that orbital Burkitt's lymphoma can be a differential diagnosis of retinoblastoma.     

Ophthalmic assessment in black patients with vitiligo

The objective of this study was to describe and estimate the prevalence of pigmentary disturbances occurring in the eyes of patients presenting with vitiligo in a teaching hospital in Ibadan, Nigeria. Patients presenting with vitiligo to the dermatology clinic of the University College Hospital between March and December 2001 were referred to the eye clinic of the same hospital for ophthalmic evaluation. Patients were assessed by visual acuity, intraocular pressure, refraction, slit-lamp biomicroscopic evaluation of the anterior segments and funduscopic examination of the two eyes. Visual fields estimation was done using the Goldman's perimeter. A total of 26 patients were referred to the eye clinic. Of these, only 17 patients were considered evaluable for the study. There were seven males and eight females. The age range was 5-30 years. The largest extent of vitiligo recorded in the study population was 25% of the body surface area. The duration of the vitiligo was two months to 3 1/4 years. None of the patients complained of any visual disturbance. All ophthalmologic assessment profiles were normal for all patients. One of the patients had poliosis. No pigmentary disturbance of the eyes was noticed in any of our patients. Pigmentary changes were not seen in these groups of blacks with vitiligo.     

CD4+CD25+ regulatory T cells mediate acquired transplant tolerance

The Holy Grail of clinical organ transplantation is the safe induction of allograft tolerance. Transplant tolerance has been successfully induced in animal models. Since T cells play a pivotal role in graft rejection, modulating T cell function has been the primary focus of studies aimed at inducing transplant tolerance. Rodent models of transplant tolerance induction include central deletion and peripheral mechanisms involving activation-induced cell death (AICD), anergy, immune deviation, and production of regulatory T cells. These mechanisms are not mutually exclusive. Although clonal deletion and anergy limit self-reactive T cells in the thymus, these mechanisms alone are not sufficient for controlling self-reactive T cells in the periphery. There is now evidence that the adult animal harbors two functionally distinct populations of CD4(+) T cells; one mediates autoimmune disease and the other dominantly inhibits it. The latter cells express CD4, CD25 and CTLA-4. These thymus-derived T cells have recently been shown to mediate the induction and maintenance of transplant tolerance. These CD4(+)CD25(+) T cells are similar in origin, phenotype, and function to those that maintain natural self-tolerance and T cell homeostasis in the periphery. Against this background, is it possible that alloantigen specific regulatory T cells might be generated and expanded ex vivo before organ transplantation and then infused to induce long-term tolerance, perhaps without the need for chronic immunosuppression?     

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

There is still no consensus on the optimal treatment of the neck in oral cavity cancer patients with clinical N0 neck. The aim of this study was to assess a possible benefit of elective neck dissection in oral cancers with clinical N0 neck. A comprehensive search and systematic review of electronic databases was carried out for randomized trials comparing elective neck dissection to therapeutic neck dissection (observation) in oral cancer patients with clinical N0 neck. A meta-analysis of the studies which met our defined selection criteria was performed using disease-specific death as the primary outcome, and the relative risk (RR) of disease-specific death was calculated for each of the identified studies. Both fixed-effects (Mantel-Haenszel method) and random-effects models were applied to obtain a combined RR estimate, although between-study heterogeneity was not found to be significant as indicated by an I(2) of 8.5% (p=0.350). Four studies with a total of 283 patients met our inclusion criteria. The results of the meta-analysis showed that elective neck dissection reduced the risk of disease-specific death (fixed-effects model RR=0.57, 95% CI 0.36-0.89, p=0.014; random-effects model RR=0.59, 95% CI 0.37-0.96, p=0.034) compared to observation. This reduction in disease-specific death rate supports the need to perform elective neck dissection in oral cancers with clinical N0 neck.     

Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells

Glycyrrhiza glabra L. (Fabaceae), commonly known as ‘liquorice’, is a well‐known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet‐tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra. Copyright © 2015 John Wiley & Sons, Ltd.     

Functional characterization of α1-adrenoceptor subtypes in the rabbit spleen

Phenylephrine and (±)N-[5-(4,5-dihydro-1-H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulphonamide hydrobromide (A 61603) evoked concentration-dependent contractions of the rabbit spleen. These contractions were antagonized by prazosin (10^–8–10^–7 M) with pA ₂ values of 8.34±0.11 and 8.15±0.10 against phenylephrine and A 61603, respectively. In both cases, the slopes of the Schild plots were not significantly (P>0.05) different from 1.0, indicating competitive antagonism. The effects of subtype-selective antagonists WB 4101 [2-(2-6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride] and 5-methylurapidil on agonist-induced contractions were also examined. WB 4101 competitively antagonized agonist-induced contractions; pA ₂ values were 8.13±0.10 and 8.10±0.03 against phenylephrine and A 61603, respectively. Corresponding values for 5-methylurapidil were 8.28±0.17 and 7.93±0.02 against phenylephrine and A 61603, respectively. Tamsulosin and Rec 15/2739 [(8-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl)-3-methyl-4-oxo-2-phenyl-4H-1-benzopyran dihydrochloride] also antagonized phenylephrine- and A 61603-induced contractions with pA ₂ values of 9.38±0.13 and 9.18±0.06 (tamsulosin) and 8.41±0.12 and 8.34±0.11 (Rec 15/2739) against phenylephrine and A 61603, respectively. HV 723 (α-ethyl-3,4,5-trimethoxy-α-(3-((2-(2-methoxyphenoxyethyl)-amino)-propyl)benzene-aceto-nitrile) fumarate) competitively antagonized phenylephrine-induced contractions with a pA ₂ value of 8.57±0.06. Chloroethylclonidine (CEC; 10^–4 M) shifted phenylephrine and A 61603 concentration-response curves to the right, reducing their potencies approximately two- to threefold, while the maximum response was reduced by 8% in both cases. It was therefore concluded that contractions of the rabbit spleen induced by α₁-adrenergic agonists were mediated predominantly by a relatively CEC-insensitive α₁-adrenoceptor subtype, possibly the α_1L-subtype. Received: 14 April 1998 / Accepted: 17 June 1998     

Zur Beeinflussung der Nahrungsaufnahme durch Psychopharmaka

Summary The effects of 16 psychotropic drugs on food intake and body weight were studied in female Wistar rats under carefully controlled conditions. After 3 days of placebo treatment the drugs were administered orally 1 hr prior to a 12-hours-per-day feeding period for at least 3 further days. Normal daily feed consumption averaged 6.11 g/100 g BW. Haloperidol, reserpine, chlorpromazine, chlorprothixene, promethazine, azacyclonol, imipramine, and amitriptyline in appropriate doses all reduced both food intake and body weight, but there were marked differences in activity. Small amounts of chlorpromazine may even stimulate feeding behaviour. Chlorpromazine sulfoxide was without influence. The central stimulant Tradon^® evoked anorexia whereas only short-lasting anorexigenic effects if any were observed following the administration of either 2-diethylamino-4-oxo-5-phenyl-oxazoline or pipradol. On the other hand chlordiazepoxide, phenobarbital, and to some extent oxazepam caused the animals to increase their feed consumption and to gain weight. The results are discussed with regard to clinical reports of appetite and weight changes due to psychotropic drugs.