Parental perception of neonatal intensive care in public sector hospitals in South Africa.

BACKGROUND: Little is known about parental experience and decision making with regard to premature infants requiring intensive care in developing countries. We undertook this study to characterise parents' experience of physician counselling and their role in making life-support decisions for very low-birth-weight (VLBW) (birth weight < 1 501 g) infants born in South Africa's public-sector neonatal intensive care units (NICUs). METHODS: Parents of surviving VLBW infants treated in three Johannesburg-area public hospitals and attending follow-up clinics in August 2001 were interviewed regarding their experience of perinatal counselling on outcomes (pain, survival, disability), perception of actual and optimal decision making, and satisfaction with NICU communication. RESULTS: Parents of 51 infants were interviewed. Seventy-five per cent of parents reported antenatal counselling by physicians on at least one perinatal topic (severe disability, pain, death, finances or religious/moral considerations). The majority of parents (> 60%) who received counselling thought that these topics had been discussed adequately. Most parents reported that doctors had the primary decision-making role, either without consulting them (41%) or after consulting them (37%). Joint decision making was rare (14%). Parents wanted more input in life-support decisions than they reported being given. CONCLUSION: Counselling is not consistently provided in public-sector hospitals in Johannesburg. Parents of premature infants want a larger share in NICU decision making than they currently experience. Most parents were satisfied with communication later during their infant's hospitalisation. South Africa presents a unique opportunity to study the use of advanced medical technologies in a nation with marked disparities in access to care.     

Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids.

Due to the high affinity of new inhaled corticosteroids (ICS) towards the glucocorticoid receptor (GR), and because of the similarities between the binding domains of the GR and the progesterone receptor (PR), the present study focused on assessing the relative binding affinities (RBA) of glucocorticoids (systemic and ICS) to PR (RBAPR). By comparison with the affinities towards the GR (RBAGR) the binding selectivities were also assessed. In general, the selectivity of the investigated glucocorticoids showed a decreasing trend with increasing lipophilicity. When orally administered, less lipophilic glucocorticoids showed the highest selectivity, with RBAGR/RBAPR ratios of 1,375, 760 and 476 for betamethasone, beclomethasone and dexamethasone, respectively. For ICS, mometasone furoate, the most lipophilic steroid, was the least selective (1.1), followed by beclomethasone monopropionate (9), fluticasone propionate (12), triamcinolone acetonide (18), mometasone (25) and budesonide (44), which shows the highest selectivity among inhaled glucocorticoids. In conclusion, the present study revealed that there are differences in selectivity among commercially available glucocorticoids. Future clinical studies are needed to investigate whether the high affinity of some of the investigated glucocorticoids to the progesterone receptor is of clinical relevance.     

Evaluation of active and passive transport processes in corneas extracted from preserved rabbit eyes

In vitro transcorneal permeability studies are an important screening tool in drug development. The objective of this research is to examine the feasibility of using corneas isolated from preserved rabbit eyes as a model for permeability evaluation. Eyes from male New Zealand White rabbits were used immediately or were stored overnight in phosphate-buffered saline (PBS) or Hanks balanced salt solution (HBSS) over wet ice. Integrity of isolated corneas was evaluated by measuring the TEER and by determining the permeability of paracellular and transcellular markers. Active transport was assessed by measuring transcorneal permeability of selected amino acids. Esterase activity was estimated using p-nitrophenyl assay. In all cases, corneas from freshly enucleated eyes were compared to those isolated from the day-old preserved eyes. Transcellular and paracellular passive diffusion was not affected by the storage medium and observed to be similar in the fresh and preserved eye models. However, amino acid transporters demonstrated lower functional activity in corneas excised from eyes preserved in PBS. Moreover, preserved eyes displayed almost 1.5-fold lower esterase activity in the corneal tissue. Thus, corneas isolated from day-old eyes, preserved in HBSS, closely mimics freshly excised rabbit corneas in terms of both active and passive transport characteristics but possesses slightly reduced enzymatic activity. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1921–1930, 2010     

Polymerisation by the chromate/arsenite system

The aqueous polymerisation of methyl methacrylate initiated by the chromate/arsenite system has been studied. It is observed that the polymerisation by the above redox system is catalysed by OH^? though the parent reaction between chromate and arsenite is catalysed by H^⊕. It is also observed that traces of Cu^2⊕ inhibit both the polymerization reaction as also the parent reaction. From these observations it is concluded (1) intermediate valency states of chromium has no initiating power in alkali solution and (2) the redox reaction between chromate and arsenite is a chain reaction involving single electron transfer and the intermediate As^4⊕ thus produced is the initiating species.     

Endotoxin-induced gamma interferon production: contributing cell types and key regulatory factors

Gamma interferon (IFN-gamma) is an important mediator of endotoxin (lipopolysaccharide [LPS])-induced immune responses. However, the specific cell types that produce IFN-gamma in response to LPS and the cellular factors that regulate LPS-induced IFN-gamma production have not been fully determined. The present studies were undertaken to characterize the cell populations that produce IFN-gamma after LPS challenge in the spleens of mice and to determine the regulatory factors that modulate LPS-induced production of IFN-gamma. Our studies show that the levels of splenic IFN-gamma mRNA and protein production peak at 6 and 8 h, respectively, after systemic LPS challenge. Approximately 60% of IFN-gamma-producing cells are natural killer (NK) cells (CD3(-)DX5(+)) and 25% are NKT cells (CD3(+)DX5(+)). Most of the remaining IFN-gamma-producing cells are T cells (CD3(+)DX5(-)), macrophages, and dendritic cells. Functionally, interleukin-12 (IL-12) is the major IFN-gamma-stimulating factor after LPS challenge, with costimulation provided by IL-15, IL-18, and B7 proteins. IL-10 is a major inhibitor of LPS-induced IFN-gamma production. Unlike intact heat-killed gram-negative and gram-positive bacteria, the class II major histocompatibility complex did not play a functional role in LPS-induced IFN-gamma production. LPS is a potent stimulus for splenic IL-10, IL-12 p40, and IL-15 mRNA expression, whereas IL-12 p35 and IL-18 mRNAs, as well as B7 proteins, are constitutively expressed in the mouse spleen. Of the factors studied, IL-18 serves as the most potent costimulus with IL-12 for IFN-gamma production, followed by IL-15 and B7 proteins. These data demonstrate that NK cells and NKT cells are the most abundant IFN-gamma-producing cells in the mouse spleen after LPS challenge and that IL-10 and IL-12 are key functional regulators of LPS-induced IFN-gamma production.     

Pharmacokinetics, in-situ absorption and protein binding studies of a new neuroleptic agent centbutindole in rats.

The present study reports the absorption kinetics, plasma protein binding and pharmacokinetic profile of the centbutindole (I) after i.v. and oral dosing in rats. In addition, an in-situ absorption study was carried out using a closed-loop technique at pH 2.6 and 7.4. The rate of absorption at pH 2.6 was 5-fold less compared to that observed at pH 7.4. In-vitro and in-vivo protein binding (ultra filtration technique) was independent of substrate concentration over a range of 1.25-10.0 microg/ml. Pharmacokinetic parameters of I were determined in male rats after administering a single 4 mg/kg oral dose and 2 mg/kg intravenous dose. The peak serum concentration of I was found to be 50.1 ng/ml at 30 min after oral administration followed by a secondary Cmax of 43.2 ng/ml at 180 min. For the hydroxy metabolite (II), a Cmax of 6.4 ng/ml was measured at 360 min after oral administration of I. After oral dosing an irregular concentration-time profile with secondary peaks was observed for both I and II. The terminal half-lives for I and II after oral dosing were 163 and 263 min, respectively. After intravenous dosing, the levels of I decreased biexponentially with a distribution (t(1/2) alpha) and elimination (t(1/2) beta) half-lives of 5.7 and 128 min, respectively. Comparison of the AUC after oral and intravenous dosing of I indicates that only about 24% of the oral dose reaches the systemic circulation. The limited bioavailability can either be due to the poor solubility of the compound and/or extensive first pass metabolism in the gastrointestinal (GI) tract. Co-administration of polyethylene glycol (PEG) at oral dosing improves solubilization and increases bioavailability.