Physical Stability of Solid Dispersions Containing Triamterene or Temazepam in Polyethylene Glycols

The effect of storage on the physical stability of solid dispersions of triamterene or temazepam in polyethylene glycols was studied using differential scanning calorimetry (DSC), particle-size analysis and dissolution methods. The enthalpies of fusion of the carriers, without included drug and previously fused and crystallized, increased on storage. Analysis of similarly treated solid dispersions, containing either 10% temazepam or 10% triamterene, showed that each drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies and melting points of the solidus components of the dispersions' carriers were initially reduced after preparation, but on storage these increased. The particle sizes of the drugs dispersed in the PEGs increased on storage. The changes in dissolution after storage of triamterene or temazepam dispersions were smaller for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was particularly marked during the first month of storage. The rank order of changes in dissolution were PEG 1500 ? PEG 2000 < PEG 4000 ～ PEG 6000.     

The allergens of dog II. Identification and partial purification of a major dander allergen

A dog hair and dander (DHD) extract was prepared from hair obtained from mixed breeds. By SDS-polyacrylamide gel electrophoresis (SDS–PAGE) and immunoblotting, using sera from 32 dog-allergic subjects, a number of IgE radio-staining bands could be seen. In 78% of sera a protein of molecular weight (MW) of 21 000 daltons, designated Ag X, was found to bind IgE and in 34% it did so strongly. This allergen was isolated from DHD by size-exclusion and ion exchange chromatography. The final product was a single allergen of MW of 21 000 and an isoelectric point of approximately 5.2. An additional protein-staining band could still be seen of MW of 24 000 daltons. Using a serum which contained IgE antibodies only to Ag X, this allergen was found only in DHD extract and dog saliva and was absent from dog serum and urine. It was the same dog allergen that we [1] reported as Ag 8 using crossed radio-immunoelectrophoresis (CRIE) and that Blands et al. [2] and Løwenstein [3] described as Ag 13. We propose that this major dog allergen be given the title Can f I according to the new allergen nomenclature.     

Pentoxifylline acts synergistically with A23187 to increase the penetration of zona-free hamster oocytes by cryopreserved human spermatozoa

The number of cryopreserved human spermatozoa which penetrated zona-free hamster oocytes afier stimulation with 2μmol A23187 per litre was increased by the hrther addition of 0.6 or 3.6 mmol pentoxifjrlline per litre. With spermatozoa prepared by washing by repeated centrifugation, the median numbers of sperm headd/egg were 1.9, 7.9 and 10.8 in the presence of 0, 0.6 or 3.6 mmol pentoxifylline per litre, respectively. A similar effect was observed with spermatozoa prepared on a Percoll gradient. As A23187 inhibited sperm motility, and this was exacerbated by pentoxifylline, the increased penetration rate of hamster oocytes cannot be explained by improved sperm motility. The number of spermatozoa stimulated to acrosome react by 2 μmol A23187 per litre was increased 3-fold by 3.6 mmol pentoxifylline per litre and 4-fold by 5 mmol caffeine per litre. These data suggest that CAMP may act synergistically with Ca²⁺ to stimulate the acrosome reaction. Pentoxifjrlline may improve the fertility of poor-quality human spermatozoa by enhancing their ability to respond to the Ca²⁺ signal produced by binding to the zona pellucida.     

Progress in Rhesus Histocompatibility Typing Resulting from the Second International Nonhuman Primate Histocompatibility Workshop (1973)

The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developd in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.     

A Novel Tertiary Pyridostigmine Derivative [3-N,N-Dimethylcarbamyloxy)-1-Methyl-{Delta}3-Tetrahydropyridine]: Anticholinesterase Properties and Efficacy against Soman

In an effort to develop an effective centrally acting pretreatmentcompound against organophosphorus poisons, the tertiary pyridostigmine(Pyr) derivative 3-(N,N-dimethyI-carbamyloxy)-l-methyl-³-tetrahydropyridine(THP) was synthesized and studied for its anticholinesteraseproperties, as well as its efficacy against soman intoxicationin guinea pigs. Injection of THP (262 µg/kg, im) intoadult male guinea pigs caused inhibition of Wood (30%) and brain(25%) acetylcholinesterase (AChE), showing that THP penetratesthe blood-brain barrier. Pyr (131 µg/kg, im) caused AChEinhibition in the Hood (59%), but not in the brain. The inhibitorypotencies of THP and Pyr were compared by determining theirIC50 values for in vitroinhibition of both AChE (brain, erythrocyte)and pseudo-cholinesterase (plasma) in three mammalian species(guinea pig, rat, rabbit). THP, although effective in inhibitingboth types of cholinesterase, was in general less potent thanPyr. Pretreatment of guinea pigs with THP (262 µg/kg,im) plus Pyr (131 µg/kg, im). 30 min prior to subcutaneoussoman challenge, with no antimuscarink or oxime treatment, protected60% of the animals against 2 ? LD50 of soman. Neither THP norPyr alone was effective. The protective pretreatment regimendid not prevent convulsions, but shortened the recovery timein surviving animals (median recovery time 1.6 hr, comparedto 24 hr in control and other groups of animals pretreated withTHP or Pyr alone). A combination of THP and Pyr thus appearsto provide a means of evaluating the relative importance ofselective peripheral plus central vs peripheral AChE protectionagainst soman.     

Muscular strength at 5 years of children with a birthweight under 1500g

Abstract The hand-grip strength was measured as part of the 5-year neurodevelopmental assessment of 24 very low birthweight (VLBW) and 18 normal birthweight (NBW) children. Hand-grip strength was significantly lower in the VLBW children for left and right hands tested individually and for both hands used concurrently. Increasing hand-grip strength was significantly related to 5-year weight percentiles and to being in the NBW group. More of the VLBW children weighed less than the 10th percentile. After adjusting for the 5-year weight percentile, the hand-grip strength of VLBW children was still significantly lower than that for NBW children. This is another aspect of development in which VLBW children are disadvantaged.