Surface-Attached Polymer Networks Made from Cationic Poly(diitaconates): Synthesis,Surface Characterization,and Bioactivity

Facially amphiphilic polymers carrying cationic and hydrophobic groups on the same repeat unit have shown promising antimicrobial activity and biocompatibility, yet they are prone to suffer from protein adhesion which may induce biofilm formation. To overcome this problem, poly(diitaconate)-based copolymers with cationic/hydrophobic and protein-repellent/charge-neutral repeat units are synthesized. The bioactivity profile of surface-attached polymer networks made from these copolymers depends on the ratio of the cationic and charge-neutral repeat units. In all cases, the protein adhesion is substantially reduced compared to purely cationic polymers. At a 50:50 ratio, the polymer coatings are partially protein-repellent and antimicrobial, yet slightly cell toxic. At an intermediate composition of 30:70, they are still antimicrobial and the cell compatibility is substantially improved. The long-term stability of these materials still has to be determined to judge their suitability for medical applications.     

The Interaction of Hydrochlorothiazide with Spirapril: A Novel Ace Inhibitor

In an open-label, randomized trial using a 3 x 3 Latin square design, single doses of 24 mg of the ACE inhibitor spirapril, or 50 mg hydrochlorothiazide, or their combination were given to 18 healthy male volunteers. No alteration in the area under plasma drug concentration curve (AUC), peak plasma level, time to peak level, or elimination half-life was detected for hydrochlorothiazide, spirapril, or its active metabolite, spiraprilat, during combination therapy. It was concluded that there was no significant effect of spirapril on single-dose kinetics of hydrochlorothiazide, nor of hydrochlorothiazide on single-dose kinetics of spirapril. Significant reductions in systolic blood pressure were noted 2--6 h after either spirapril or combination treatment, but no evidence of any synergistic effect of single-dose effects on blood pressure was seen during combination therapy.     

A strategy for reducing maternal mortality

A confidential system of enquiry into maternal mortality was introduced in Malaysia in 1991. The methods used and the findings obtained up to 1994 are reported below and an outline is given of the resulting recommendations and actions.     

Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia: the role of sensitization

A number of consistent clinical observations provide direction for the hypothesis that pathological sensitization of neuronal systems may be an important factor for relapse or the onset of stimulant-induced psychosis (eg, methamphetamine or amphetamine psychosis, cocaine psychosis and phencyclidine psychosis) and schizophrenia. First, psychotic symptoms can be produced in normal subjects by stimulants. Secondly, a large portion of schizophrenic patients exhibit exacerbation of psychotic symptoms in response to stimulants at doses which would not be psychotogenic in normal subjects. Lastly, the ability of stress to precipitate the onset and relapse of schizophrenia is well documented. In this regard, acute responses to stimulants provide useful information for relapse prediction of schizophrenia and substance abuse. This paper addresses the nature and role of pathological sensitization in relapse of stimulant- and phencyclidine-induced psychosis and schizophrenia, and its relation to pathophysiology of schizophrenia.     

Neutropenia with fever

CAUSAL GERMS: Over the last 10 years, hemotology units have seen many changes in the epidemiological pattern of infections in neutropenic patients, with a growing number of infections caused by Gram-positive germs. The number of septicemias due to multiresistant Gram-negative germs (Pseudomonas aeruginosa, Strenotrophomonas maltophilia) has however remained high. IMPACT OF THERAPEUTIC REGIMENS: Improved prognosis in neutropenic patients depends for a large part on careful management of septic episodes. As the risk of septicemia is strongly correlated with the degree of efficacy of antibiotic regimens, susceptibility data must always be examined when developing antibiotic protocols in units caring for neutropenic patients.     

Mega-Liposuction: Analysis of 1520 Patients

Fifteen hundred and twenty cases of liposuction/liposculpture were performed at Dr. M. Erfan & Bagedo Hospitals and King Abdulaziz University Hospital in Jeddah from January 1983 to December 1994. These cases were mostly females. The age group was from 16–65 years. Multiple procedures were performed in 11.68% of these cases. The change in hemoglobin and the hematocrit ratio pre- and post-operatively, and the incidence of complications, were studied. The percentage of surface area operated upon rather than the amount of fat removed was the most important relevant factor.     

Health in India -- a futuristic scenario

There has been considerable progress in the health situation in India over the last five decades following its independence. Mortality decreased dramatically, the death rate declined from 27.4 to 8.9, and the infant mortality rate decreased by almost half in 1997. Life expectancy, on the other hand, almost doubled from 32 years at the time of independence to 62 years in 1997. However, there are wide variations in the values of these health indicators among different regions. Progress has been uneven and confined to more advanced states. Improvements in the health status of the people have been most notable in the states of Kerala, Maharashtra, and Punjab, whereas states like Madhya Pradesh, Uttar Pradesh, Orissa and Rajasthan had the least progress. These neglected areas are considered as the result of various factors in India's political economy, which hinders health policy development and its implementation. In the last part of this article, major health problems, as well as recommendations for remedial actions are outlined.     

Pharmacokinetic Analysis and Antiepileptic Activity of Tetra-Methylcyclopropane Analogues of Valpromide

Purpose. The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetra-methylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics. Methods. The study was carried out by investigating the pharmacokinetics in dogs and pharmacodynamics (anticonvulsant activity and neurotoxicity) of the following three cyclopropane analogues of VPD: 2,2,3,3-tetramethylcyclopropane carboxamide (TMCD), N-methyl TMCD (M-TMCD) and N-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-glycinamide (TMC-GLD). Results. The three investigated compounds showed a good anticonvulsant profile in mice and rats due to the fact that they were metabolically stable VPD analogues which were not biotransformed to their non-active acid, 2,2,3,3-tetramethylcyclopropane carboxylic acid (TMCA). M-TMCD was metabolized to TMCD and TMC-GLD underwent partial biotransformation to its glycine analogue N-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-glycine (TMC-GLN). Unlike TMC-GLN, the above mentioned amides had low clearance and a relatively long half life. Conclusions. In contrast to VPD which is biotransformed to VPA, the aforementioned cyclopropane derivatives were found to be stable to amide-acid biotransformation. TMCD and M-TMCD show that cyclic analogues of VPD, like its aliphatic isomers, must have either two substitutions at the position to the carbonyl, such as in the case of TMCD, or a substitution in the and in the positions like in the VPD isomer, valnoctamide (VCD). This paper discusses the antiepileptic potential of tetramethylcyclopropane analogues of VPD which are in animal models more potent than VPA and may be non-teratogenic and non-hepatotoxic.