Pharmacokinetics of peptide T in patients with Acquired Immunodeficiency Syndrome (AIDS)

1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration.

2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA.

3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.     

Potent gp120-like neurotoxic activity in the cerebrospinal fluid of HIV-infected individuals is blocked by peptide T.

The envelope protein of the human immunodeficiency virus (gp120) causes neuronal death in developing murine hippocampal cultures or rat retinal ganglion cells. In HIV-infected individuals, gp120 released from HIV-infected macrophages or other cells in the brain has been proposed as the etiology for the pathophysiology of AIDS central nervous system (CNS) disease by diffusing to act at a distance to cause damage and/or death to neighboring neurons. In this study, 28 cerebrospinal fluid (CSF) samples from HIV-infected individuals (79% were WR stage 1 and 2) and neurological disease controls were tested, blind to the investigator, for the presence of in vitro neuronal killing activity. Neurotoxic activity was detected with peak effects at a 1:10(5) dilution in CSF from 9/18 HIV-infected individuals and 1/10 neurological disease controls. Thus half of CSF from early stages of HIV disease are characterized by the presence of neurotoxic activity which is not present in control CSF (Fischers exact test, P < 0.05). The neuronal toxicity by patient CSF could be prevented by peptide T (1 nM). A monoclonal antibody to mouse CD4, RL.172, also attenuated or prevented CSF-induced neuronal killing in all four CSF samples tested. In addition, an antiserum to peptide T previously shown to bind gp120 and neutralize both infectively and direct gp120 neurotoxicity, neutralized the CSF factor. gp120, or a modified small fragment, is suggested to be the responsible toxic molecular entity. These results may be relevant to the pathophysiology of HIV-related CNS disease and the mechanism by which peptide T causes improvements.     

Perspectives on the Mechanism of Action of Electroconvulsive Therapy: Anticonvulsant, Peptidergic, c-fos Proto-oncogene Effects

Although the mechanism of action of electroconvulsive therapy (ECT) in affective illness has remained elusive, it is hoped that the consideration of mechanisms underlying the anticonvulsant efficacy of ECT will provide new insights into its biochemical and neuroanatomical substrates. In the amygdala-kindling model, electroconvulsive seizures (ECS) inhibit both the development and completed phases of kindled seizure evolution, and therefore, ECS is a more potent anticonvulsant modality than carbamazepine, which inhibits only completed kindled seizures. Carbamazepine is increasingly recognized for its acute and prophylactic efficacy in bipolar affective illness. Thus, comparing and contrasting effects of ECS and carbamazepine may provide insights into overlapping mechanisms of anticonvulsant and psychotropic action. Anticonvulsant effects of ECS have been most closely linked to endogenous opiate substances, perhaps acting on delta-opiate receptors, but a wide variety of other neurotransmitter and peptidergic effects are also potential candidates. Electroconvulsive seizures in mice activate the proto-oncogene c-fos in many discrete areas of brain, including a variety of limbic sites, the ventromedial nucleus of the hypothalamus, and the cerebellum. As such, c-fos induction may provide both an anatomical map of areas potentially activated by ECS and a potential mechanism for initiating a sequence of events that may be important to the mechanism of action of ECT. Although the anticonvulsant effects of ECT may ultimately prove to be separable from those mediating its therapeutic effects in affective illness, seizures and anticonvulsant effects provide easily measurable endpoints for preclinical and clinical studies. Given this clarity of effect, potential anticonvulsant mechanisms can rapidly be identified, enabling direct testing of whether or not these same mechanisms are also critical to the therapeutic effects of ECT in affective illness.     

Detection of hepatitis B antibody by a single-antibody radioimmunoassay.

A radioimmunoassay (RIA) for the measurement of antibody to hepatitis B surface antigen (anti-HB-s) in human and non-human sera is described. The principle is based upon our earlier observation that anti-HB-s and hepatitis B surface antigen (HB-s-Ag) are soluble in 4.5% w/v polyethylene glycol 4000 but that anti-HB-s-HB-s-Ag complex is precipitated. The use of activated charcoal suspended in polyethylene glycol and dextran solution facilitated the separation of this complex by centrifugation, thus improving reproducibility and sensitivity. The test is approx. 3-5000 times as sensitive as counterelectrophoresis. In a survey of a normal blood donor population, with an incidence of approx. 0.1% positive for HB-s-Ag by RIA, 7-8% were found to have anti-HB-s by this method.     

Nicotine and smoking: Effects upon subjective changes in mood

A Mood Adjective Check List and an activation scale were used to measure subjective reports on mood changes in 24 male habitual smokers before and after smoking cigarettes with known content of nicotine, at different times of day and rates of puffing. Ratings on pleasantness were dose related. Aggression and anxiety showed effects attributable to circadian influence and slight decreases in both factors occurred after smoking the highest nicotine cigarette. The MACL scores were greatly affected by the experimental procedure. Levels of inner tension were found related to the nicotine inhaled. The heuristic value of the concept of activation in these studies is suggested.This work was supported by the Tobacco Research Council, and carried out at the Institute of Psychiatry, London.     

An immune hemagglutination procedure with very high sensitivity applied to the detection of hepatitis B antibody and antigen and immune complex.

An immune agglutination procedure is described in which red cells are coated with antigen and agglutination is observed after a short incubation with antibody in reagent serum. Conversely, the cells may be coated with antibody and used to test for the presence of antigen. Treatment of the reagent serum with cobra venom factor results in inhibition, and there is a marked lo-s of sensitivity with cells pretreated with formalin or chromic chloride, suggesting that C3 and some type of reactive sites on the cells are required. The distinctive features of the new procedure are that incubation time is very short, sensitivity is several orders of magnitude higher than with other related tests, and, within some limitations, bovine (steer) red cells with bovine serum can be used as an alternative to human red cells with human serum. It is necessary to remove an inhibitor from the reagent serum, human or steer. While the mechanism of the procedure needs further elucidation, the findings reported here suggest that it ought to be sufficiently sensitive to detect hepatitus B antigen if present in virtually any blood sample. With appropriate modifications it should be useful for blood donor screening, diagnosis, and for studying many other antigen-antibody systems.     

Surgery of congenital clubfoot in Don Orione, Health Center for physical handicaps of Ivory Coast (About 554 feet)

OBJECTIVES: Treatment of congenital clubfoot improved in occidental country. We have studied the epidemiology, clinical and therapeutic aspects of this malformation in the context of Africa. PATIENTS AND METHODS: This was a retrospective study. Two thousand five hundred and sixty-two patients were hospitalised and operated during 12 years, 362 of them were diagnosed with congenital clubfoot. This represented 14,1% of the surgical diseases, with an incidence of 30,2 cases per year. The male to female ratio was 1,6:1, and ages ranged from 4 months to 38 years old, 59% of which were less than 15 years old. Two hundred and four (56,3%) patients had bilateral disease, 93 (25,7%) had right side disease and 65 (18%) had left sided disease. Considering the classification types we noted in our patient population 82% type III, 5% type II, 3% type I and 10% were undefined. RESULTS: Posteromedial approach describe by Codivilla was used in 45,5% of cases. Codivilla approach associated with lateral access to the foot in 44,4% of cases, with dorsal access in 2,3%. Few patients (7,8%) have had another approach. One hundred and seventeen patients received physiotherapy prior, but all the patients operated have postoperative physiotherapy while wearing orthopaedic shoes. Results obtained were: good in 510 cases (92%), quite good in 35 cases (6,3%), fairly good in 7 cases (1,3%) and mediocre in 2 cases (0,4%). CONCLUSION: The surgical aspect is still only a fraction of the entire treatment. It is imperative that physiotherapy is started immediately and orthopaedic shoes be worn postoperatively.     

Recurrence of left atrial myxoma mimicking a mitral annuloplasty ring thrombosis

Cardiac myxomas (CM) is by far the most common type of primary cardiac neoplasm that commonly arise within the left atria and is composed of primitive connective tissue cells and stroma. Despite the benign nature, the CMs are often surgically removed because they can lead to severe complications. Large, thin, and hypermobile forms are unusual. The frequency of recurrence is about 22% for complex forms and 12% for other familial forms and 1% to 3% for sporadic myxomas, which seldom recur after surgery. Although transesophageal echocardiography shows usually accurate imaging capabilities to detect the myxoma, further imaging methods including computed tomography, cardiovascular magnetic resonance imaging, and ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography may be useful to diagnosis for it. Surgery is the mainstay of treatment     

Hygiene practices in abattoir and slaughter slab,determinants and assessment of abattoir and slaughter slab facilities in Abakaliki,Ebonyi State South-East Nigeria

BackgroundWorkers in slaughterhouses engaging in unhygienic practices create conducive environments for zoonoses and meat contamination. Knowledge of hygiene practices and their determinants provides evidence for the design of targeted interventions.ObjectivesWe investigated knowledge and determinants of hygiene practices among workers in slaughterhouses and assessed slaughterhouse facilities in Abakaliki.MethodsWorkers in the Central Meat Market abattoir and Slaughter slab Abakaliki were interviewed in a cross-sectional quantitative study to ascertain their knowledge and hygiene practices while abattoir facilities were assessed using a checklist. Associations were analysed with Chi-square while predictors were determined using binary logistic model.ResultsWe interviewed 188 workers 75.5% and 85.6% of whom had good knowledge and good hygiene practices respectively. However, hand-washing before and after handling meat (44.1%), cleaning work surfaces with soap and water (45.2%) and sanitary disposal of waste (6.9%) were suboptimal. Knowledge of good hygiene practice was a predictor of good hygiene practice (AOR: 4.6, 95% CI: 2.0–11.3, p=0.001). Well water and borehole were present in both slaughterhouses and cold rooms were available in Central Meat market abattoir.ConclusionsThe level of good knowledge was high and this was a determinant of good hygienic practices. Training on hygiene practices is recommended to prevent meat contamination and zoonoses.     

Kinetics of oxygen reduction on gold nanoparticle/multi-walled carbon nanotube hybrid electrodes in acid media

In this paper, the electrochemical reduction of oxygen has been studied on gold nanoparticle/multi-walled carbon nanotube (AuNP/MWCNT) modified glassy carbon (GC) electrodes in 0.5 M H₂SO₄ using the rotating disk electrode (RDE) method. The AuNP/MWCNT catalysts were prepared by chemical deposition of AuNPs onto MWCNTs spontaneously grafted with 4-nitrophenyl groups. The composite electrode was characterised by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV). The oxygen reduction behaviour of these electrodes was compared with that of a bulk gold electrode. The AuNP/MWCNT catalyst showed a pronounced electrocatalytic activity towards O₂ reduction in acid media. The half-wave potential of O₂ reduction on the AuNP/MWCNT catalyst shifted ca 80 mV to more positive potentials as compared to that of a polished Au electrode. The kinetic parameters of oxygen reduction were determined and the specific activity of the hybrid electrode was slightly higher than that of the bulk Au electrode.