Defining a holistic pain-relieving approach to wound care via a drug free polymeric membrane dressing.

Wound care practice continuously demonstrates that healing cannot be adequately controlled if a patient's experience of pain is not managed effectively. Current pain management guidelines do not account for the holistic treatment of pain emanating from a wound-an environment of uncontrolled or rogue inflammation, neuropathy and neuroischaemia. This article investigates how polymeric membrane dressings can interact with the pathology of wounds to correct abnormalities in pain pathways of the nervous system and dampen problematic ongoing pain to enhance the clinical picture of wound healing.

The stimulation of bioluminescence in Photobacterium leiognathi as a potential prescreen for antitumor agents.

The stimulation of bioluminescence in Photobacterium leiognathi has previously been described as a test for genotoxic compounds. An adaptation of this procedure has been developed which uses a dim variant of P. leiognathi and permits the prescreening of microbial fermentation broths for potential antitumor agents. Bioluminescence in this organism was stimulated by compounds which bind to DNA or affect DNA synthesis. Antibiotics with target sites such as protein, cell wall or RNA synthesis, did not alter bioluminescence. Fermentation broths from over 5,000 soil isolates were prescreened in this assay and 95 (1.6%) were defined as active. Further analysis of selected cultures suggested that about half produced compound(s) with DNA-binding activity. These results suggest that the photobacterium induction assay (PIA) may be useful as a prescreen for potential antitumor agents. The assay is rapid, simple and requires only microgram quantities of material for testing.

Binding of insulin by monkey and pig hypothalamus.

Membrane preparations from monkey and pig hypothalami bound [125I]insulin specifically. The binding appeared to be greater by preparations from anterior than posterior portions of the pig hypothalamus. Binding was time dependent, and its dissociation was first order with a half-time at 22 degrees C of 14 min. Desalanine insulin was as effective as native insulin in inhibiting the binding of [125I]insulin, while proinsulin was less effective and desoctapeptide insulin still less effective in accord with their biologic activities. Binding by membranes from cortex and thalamus appeared to be less than from hypothalamus. [125I]insulin was infused into an arterial split monkey brain preparation to determine if insulin that was blood borne bound specifically to the primate hypothalamus. Half the brain was perfused with [125I]insulin alone and the other half with [125I]insulin plus an excess of unlabeled insulin. Radioautography showed specific binding of insulin localized to the median eminence, infundibular nucleus, and microvessels. Thus, the monkey and pig hypothalami bind insulin with characteristics similar to those reported for known target tissues for insulin. Furthermore, insulin from the blood stream binds to specific anatomical structures in the hypothalamus of the monkey.

In situ subcellular distribution and metabolism of progesterone, estradiol and androstenedione in the vascularly separated and isolated hypothalamus of the female rhesus monkey.

A neurosurgical procedure has been developed for the vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. The circulation to the left and right halves of the hypothalamus was also isolated and each half of the hypothalamus was perfused simultaneously, but separately, with a dextran-blood solution which contained radioactive gonadal steroids. The hypothalamus in situ efficiently converted [3H]androstenedione to [3H]estrone and this aromatization was inhibited by the presence of androsta-1,4,6-triene-3,17-dione (ATD) in the perfusate. [3H]Progesterone was metabolized predominantly to 5 alpha-pregnane-3,20-dione (5 alpha-DHP) and 20 alpha-hydroxypregn-4-ene-3-one (20 alpha-OHP). Subcellular fractionation of the hypothalamus after the in situ perfusion with [3H]-progestin or [3H]estradiol to the hypothalamus of estrogen-treated ovariectomized monkeys or oil-treated ovariectomized monkeys, respectively, indicated that the retention of [3H]estradiol in the nucleus was a saturable, limited-capacity phenomenon. No saturable subcellular distribution of [3H]progesterone or [3H]R 5020 was observed. This latter observation might be attributable to the presence of a progesterone receptor in too small a concentration to be detected by the methods used.

In situ estradiol and progestin (R5020) localization in the vascularly separated and isolated hypothalamus of the rhesus monkey.

A neurosurgical procedure has been developed for vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. Utilizing this preparation, the left and right halves of the hypothalamus were perfused simultaneously, but separately, with a dextran-blood solution. Radiolabeled steroids were directly perfused in the dextran-blood into either the left or right half of the hypothalamus. Studies with radiolabeled gonadal steroids indicate that the majority of the carotid circulation is confined to the hypothalamus-thalamus area in this brain preparation and the cross-circulation of labelled steroids between the left and right sides of the hypothalamus is less than 10%. The usefulness of the preparation is illustrated by an autoradiographic study of the in situ hypothalamic distribution of (3H)estradiol in ovariectomized rhesus monkeys and of the synthetic progestin(3H)R5020 in estrogen-primed, ovariectomized rhesus monkeys. The direct perfusion of the (3H) steroids into the hypothalamus greatly increases the sensitivity of such compared to systemic administration of the (3H) steroids. The perfusion of one-half of the hypothalamus with )3H) steroid and the other half with (3H) steroids. The perfusion of one-half of the hypothalamus with (3H) steroid and the other half with (3H) steroids. The perfusion of one-half of the hypothalamus with (3H) steroid and the other half with (3H)steroid plus radioinert steroids permits in 1 animal, acting as its own control, the examination of a saturable distribution of a gonadal steroid in the rhesus monkey hypothalamus.

The metabolic clearance rate, head and brain extractions, and brain distribution and metabolism of progesterone in the anesthetized, female monkey (Macaca mulatta).

The brain distribution and metabolism of progesterone were studied in female, rhesus monkeys. Adult monkeys were anesthetized with ketamine and were given a constant infusion of [3H]- or [14C] progesterone. Blood samples were obtained from cannulae inserted into the carotid artery, the jugular vein and lateral (transverse) sinus. The metabolic clearance rate of progesterone was 295 +/- 49 (S.E.) 1/day. The head extraction of progesterone was 30.4 +/- 8.3% (S.E.) and the brain extraction 26.0 +/- 9.18% (S.E.). The peripheral conversion ratios of progesterone to 20alpha-hydroxypregn-4-en-3-one (20alpha-OHP) and 5alpha-pregnan-3,20-dione (5alpha-DHP) were 10.0 +/- 1.3% (S.E.) and 2.4 +/- 0.3% (S.E.), respectively. These same conversion ratios for across the head were 4.8 +/- 1.0% (S.E.) and 1.5 +/- 0.6% (S.E.) and for across the brain 5.0 +/- 0.7% (S.E.) and 2.2 +/- 0.6% (S.E.). The concentration of radioactive progesterone was 2-5 times higher in brain tissues compared to the carotid arterial blood. The tissue concentrations of radioactive progesterone compared to a cerebrum 'control' sample: was lower in the central gray (P less than 0.05); were the same for the amygdala, hippocampus, preoptic-anterior hypothalamus, cerebellum, hypothalamus, thalamus, and anterior pituitary; and were higher in the cervical spinal cord, optic chiasm, mesencephalon, medulla oblongata and pons (P less than 0.1). The distribution pattern of 20alpha-OHP formed from progesterone was similar to that of progesterone. 5alpha-DHP formed from progesterone had a different distribution than progesterone, being highest in the central gray area. High concentrations of 5alpha-DHP were also observed in the mesencephalon, medulla oblongata and hypothalamus and low values in the anterior pituitary. Infusions of [3H]20alpha-OHP and [3H]5alpha-DHP were used to evaluate the in vivo metabolism of progesterone by different brain areas. [3H]Estradiol infused into one monkey had its highest concentration in the anterior pituitary which was 20 times higher than in the carotid arterial blood.

Estrogen formation by the isolated perfused rhesus monkey brain.

Perfusion of two isolated brains from immature male rhesus monkeys with [(3)H]androstenedione resulted in the identification of free and conjugated [(3)H]estrone and free [(3)H]estradiol from the perfusates. In the dissected cerebral tissues, estrogens were recovered only from the hypothalamus and limbic system. The production of estrogens from androstenedione during the 40-minute perfusions in these two experiments totaled 1.58 and 2.83 nanograms.

Effect of potassium supplements on the exchangeable potassium in chronic heart disease.

A study of the effect of additional oral potassium on the low body potassium of seven patients with severe valvular heart disease showed that the potassium supplements were retained. After one month's treatment the exchangeable potassium was significantly increased, but the predicted value was not reached in any of the patients. There was no significant change in plasma potassium. These results suggest that it is of benefit to increase the dose of oral potassium for at least one month preoperatively in patients undergoing cardiac surgery.