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Optical method.

I have traced the development of the optical method from Millikan's colorimetry of cat muscle myoglobin to today's high-frequency laser diode time-resolved phase modulation system study of hemoglobin and myoglobin in muscle and brain in adult humans. The path length as well as specific absorption information is obtained in terms of the rate of photon decay or by equivalent measurements using phase modulation. Localization of inhomogeneities of deoxyhemoglobin concentrations in stroke and head injury appears possible.

Animals↗

Perfluoropolyethers in the prevention of irritant contact dermatitis.

BACKGROUND: Perfluoropolyethers (PFPEs) are non-reactive perfluorinated (no hydrogen atoms) liquid polymers that showed promise as ingredients of protective preparations in occupational dermatology. OBJECTIVE: The aim of this study was to investigate if oil-in-water (o/w) emulsions containing 0.5, 1.0, 2.0 and 4.0% PFPEs (molecular weight 6,250 D) prevent epidermal barrier disruption induced by a repetitive irritation test (RIT). METHODS: PFPE-containing o/w emulsions and the emulsion base alone were evaluated against a set of 4 irritants [10% sodium lauryl sulphate (SLS), 0.5% sodium hydroxide (NaOH), 15% lactic acid (LA), and undiluted toluene (TOL)] in the RIT. Ten subjects were tested on the paravertebral skin of the mid-back. Irritation was assessed by visual scoring, transepidermal water loss (TEWL) and colorimetry. RESULTS: Both the emulsion base and all PFPE-containing preparations significantly suppressed irritation by SLS and NaOH. Against LA and TOL, only the 4% PFPE-containing preparation was significant as assessed by TEWL. CONCLUSION: A 4% PFPE-containing o/w emulsion significantly inhibits irritation due to a wide spectrum of hydrophilic and lipophilic irritants. o/w emulsions with lower concentrations of PFPE are also effective against SLS and NaOH, but this is also true for the cream base alone. Therefore, further studies are necessary to evaluate if a minimum of 4% PFPE in the base provides additional benefit.

Caustics↗

An experimental study of the interleukin 1 levels in aqueous humor after intraocular lens implantation.

This paper studies the interleukin 1 (IL-1) levels in aqueous humor after intraocular lens (IOL) implantation in rabbits and discusses the effect of IL-1 on postoperative anterior ocular inflammation. Twenty-seven pigmented rabbits were divided into three groups: in the first group, the IOL were placed in the capsular bag after lens extraction; in the second, the lenses of rabbits were removed without IOL implantation, and the third served as the control group without surgical intervention. On the 1st, 3rd, 7th and 14th postoperative days, aqueous humor samples were obtained. MTT colorimetry was employed to detect the presence of IL-1. The data were closely studied by means of analysis of variance with SAS software. The IL-1 level in aqueous humor reached its maximum on the 14th postoperative day in the IOL-implanted group, and the IL-1 levels in aqueous humor were significantly higher (p < 0.05) on the 1st, 3rd, 7th and 14th days postoperatively in the IOL-implanted group than in the non-surgical-intervention group and extracapsular-lens-extracted group. The result suggests that there is a physical relation to the IOL itself, a relation that induces the secretion of IL-1. The result, however, is also likely to have merely come from the mechanical factors related to the presence of the IOL itself.

Animals↗

Penetration enhancers assessed by corneoxenometry.

Chemical enhancers abating the barrier function of the stratum corneum act in a number of ways. Their relative effects in mixtures are notoriously difficult to determine. Corneoxenometry is a bioassay where xenobiotic interactions with corneocytes are assessed using reflectance colorimetry. It was used to evaluate comparatively the effects of ethanol and laurocapram at various dilutions. In addition, a 10% propylene-glycol-based gel supplemented with N-acetyl-L-cysteine, urea and salicylic acid in various concentrations was tested. The relative index or irritancy (RII) was calculated for each formulation. RII is a surrogate marker of lipid removal and disorganization, and of protein denaturation in the stratum corneum. It is likely a good predictor for barrier function alterations and represents a cheap and rapid alternative to animal testing.

Acetylcysteine↗

Differential activation of p42ERK2 and p125FAK by cholecystokinin and bombesin in the secretion and proliferation of the pancreatic amphicrine cell line AR42J.

BACKGROUND: AR42J rat pancreatic acinar carcinoma cells have retained the potential to secrete digestive enzymes in addition to their ability to proliferate upon stimulation with regulatory peptides. We investigated the involvement of p42ERK2 and p125FAK (extracellular signal-regulated protein kinase and focal adhesion protein kinase, respectively) by cholecystokinin and bombesin stimulation with regard to secretion and mitogenesis. METHODS: The p42ERK2 activity was measured by kinase assay and the activation of p125FAK by antiphosphotyrosine Western blot analysis of p125FAK immunoprecipitates. The expression of both kinases was determined by Western blot analysis, the amylase secretion by colorimetry, and the DNA synthesis by [3H]thymidine incorporation. RESULTS: p42ERK2 and p125FAK were activated by cholecystokinin and bombesin with maximum stimulation at concentrations above 10 nM. Bombesin was a weaker activator of p42ERK2 and p125FAK, causing only half of the kinase activity induced by stimulation with cholecystokinin. PD98059 was shown to inhibit p42ERK2, while tyrphostin 25 blocked p125FAK tyrosine phosphorylation. Preincubation of AR42J cells with PD98059 or tyrphostin 25 was without influence on cholecystokinin- or bombesin-stimulated secretion in normal or 72-hour dexamethasone-pretreated cells. In contrast, inhibition of both protein kinases leads to reduced cholecystokinin-stimulated [3H]thymidine incorporation rates. CONCLUSIONS: Cholecystokinin induced proliferation of AR42J cells by strong activation of p42ERK2 and p125FAK. Bombesin failed to stimulate DNA synthesis, probably due to its reduced potency to stimulate these kinases. Both protein kinases are not implicated in the process of enzyme secretion.

Animals↗

Beneficial effects of softened fabrics on atopic skin.

There is general concern about the possible cutaneous adverse effects of wearing garments treated with household laundry products, particularly on atopic skin. Our objective was to compare softened and non- softened fabrics in a forearm wet and dry test, under conditions simulating real-life conditions. Twenty atopic volunteers entered a single-blind 12-day (3 sessions per day) forearm wetting and drying test. Cotton fabrics were machine washed and liquid fabric conditioner was added or not to the final rinse. To simulate conditions of skin damage, a dilute solution of sodium lauryl sulphate was applied under occlusion to the forearm of each volunteer before the start of the study. Skin effects were evaluated by visual grading (redness, dryness and smoothness), squamometry and in vivo instrumental measurements (capacitance, transepidermal water loss and colorimetry). Rubbing of atopic skin with fabrics generally resulted in discrete to moderate alterations of the structure of the stratum corneum. Both for control and pre-irritated skin, all measured parameters indicated that softened fabric was less aggressive to the skin than unsoftened fabric. In the case of pre-irritated skin, the recovery of the skin was significantly faster when rubbed with softened than with unsoftened fabrics. In conclusion, softened fabrics help mitigate the skin condition in atopic patients.

Adult↗

Mitochondria of retinal Müller (glial) cells: the effects of aging and of application of free radical scavengers.

Age-related changes of mitochondria were studied in Müller (retinal glial) cells from guinea pigs fed with or without externally applied Ginkgo biloba extract EGb 761, an established radical scavenger. When Müller cell mitochondria from aged animals were compared with those from young adults, they displayed (1) a diminished number of well-defined cristae at the ultrastructural level, (2) a reduced membrane potential, as revealed by fluorimetry using the voltage-sensitive dye tetramethyl rhodamine methylester, and (3) a slightly reduced index of vitality assayed by tetrazolium salt colorimetry. Müller cell mitochondria were also studied in aged guinea pigs which had been fed daily by EGb 761 during the last 2 months before they were sacrificed. Such mitochondria displayed (1) many well-defined cristae at the ultrastructural level, and, compared with mitochondria from untreated aged animals, (2) a significantly enhanced membrane potential and (3) a significantly enhanced index of vitality. No age- or drug-related changes were observed in the mitochondrial content of GABA transaminase, as revealed by immunocytochemistry/densitometry. These results suggest that many but not all structural and functional parameters of aging Müller cell mitochondria are impaired by accumulating oxidative damage, and that externally applied radical scavengers may protect the organelles from the damaging actions of free radicals. As it has been shown earlier that EGb 761 treatment enhances the intrinsic glutathione content of aged guinea pig Müller cells, the protective radical-scavenging effect of the drug may be mediated both directly and indirectly.

4-Aminobutyrate Transaminase↗

Amniotic fluid prealbumin as a potential marker of fetal abnormalities.

Normal amniotic fluid prealbumin (PAB) levels between 16 and 41 weeks of pregnancy are demonstrated in 175 samples from various gestational ages. PAB was measured quantitatively by immunonephelometry and qualitatively estimated by electrophoresis while total protein content was measured by colorimetry. The percent of PAB values in the total protein content is inversely correlated to the gestational age. Fetal abnormalities and abnormal conditions in pregnancy diagnosed in the second trimester and early third trimester (16-32 weeks) show significantly (p < 0.01) higher than expected PAB values (25.9 +/- 4.6 mg/l, range 19.5-35.6, n = 23) in comparison to normal fetuses and normal pregnancies of the same age (13.6 +/- 3.6 mg/l, range 4.3-19.8, n = 87). The remaining 65 samples of normal third trimester amniotic fluid were evaluated in comparison to the second trimester normal values, and inverse correlation in respect to advancing pregnancy was observed. PAB values were corrected for the total protein content and the resulting ratio had the lowest variation compared to PAB and total protein values. It is proposed that PAB, although not specific for a particular disorder, expressed as a ratio of the total protein content is a potential biochemical marker for certain fetal defects and complications of pregnancy.

Amniotic Fluid↗

Prediction of genetic risk for hypertension.

Although genetic epidemiological studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. Large-scale association studies that examine many gene polymorphisms simultaneously are required to predict genetic risk for hypertension. The population of the present study comprised 1940 unrelated Japanese individuals, including 1067 subjects with hypertension (574 men, 493 women) and 873 controls (533 men, 340 women). The genotypes for 33 single nucleotide polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed that 2 polymorphisms (825C-->T in the G protein beta3 subunit gene and 190G-->A in the CC chemokine receptor 2 gene) were significantly associated with hypertension in men and that one polymorphism (-238G-->A in the tumor necrosis factor alpha gene) was significantly associated with hypertension in women. These results suggest that 2 and 1 genes may be susceptibility loci for hypertension in Japanese men and women, respectively, and that genotyping of these polymorphisms may prove informative for prediction of the genetic risk for hypertension.

Aged↗

Nitric oxide in renal cortex and medulla. An in vivo microdialysis study.

This study examined the production of nitric oxide (NO) in the renal cortex and medulla through the use of an in vivo microdialysis technique. Oxyhemoglobin (OxyHb) at a concentration of 3 mumol/L was perfused through the dialysis system to trap tissue NO. Methemoglobin (MetHb), which was formed by NO oxidation of OxyHb in the dialysate, was spectrophotometrically assayed at 401 nm. Because the oxidation of OxyHb to produce MetHb is stoichiometric with NO, the production of NO can be determined by the rate of MetHb formation. We found that NO concentration was significantly higher (P < .05) in the medulla (57.1 +/- 5.57 nmol/L, n = 10) than in the cortex (31.2 +/- 5.7 nmol/L, n = 9). The minimal detectable NO level of this assay is approximately 10 nmol/L. Intravenous infusion of L-arginine (3 mg/kg per minute) for 30 minutes produced a twofold to three fold increase in cortical and medullary NO; NG-nitro-L-arginine methyl ester (L-NAME) (10 micrograms/kg per minute) decreased NO by 33% in the renal cortex and by 46.5% in the renal medulla. We have also compared under the same conditions the degradation products of NO, nitrite, and nitrate in the renal cortex and medulla using in vivo microdialysis combined with microtiter plate colorimetry. Nitrite/nitrate concentration was significantly higher (P < .05) in the medulla (2.7 +/- 0.6 mumol/L, n = 4) than in the cortex (2.1 +/- 0.2 mumol/L, n = 4). Infusion of L-arginine increased cortical and medullary nitrite/nitrate by 65% and 39%, respectively. L-NAME reduced cortical and medullary nitrite/nitrate by 18% and 23%, respectively. The results indicate that the OxyHb-NO microdialysis trapping technique is a highly sensitive in situ method for detecting regional tissue NO concentration and changes in the NO synthase activity in the kidney. These studies have shown that NO concentration is higher in medullary tissue than in the cortex.

Animals↗

Development of high-density DNA microarray membrane for profiling smoke- and hydrogen peroxide-induced genes in a human bronchial epithelial cell line.

Development of the high-density DNA microarray technique permits the analysis of thousands of genes simultaneously for their differential expression patterns in various biological processes. Through clustering analysis and pattern recognition, the significance of differentially expressed genes can be recognized and correlated with biological events that may take place inside the cell and tissue. With this notion in mind, high-density DNA microarray nylon membrane with colorimetry detection was used to profile the expression of smoke- and hydrogen peroxide-inducible genes in a human bronchial epithelial cell line, HBE1. On the basis of the time course of expression, at least three phases of change in gene expression could be recognized. The first phase is an immediate event in response to oxidant injury. This phase includes induction of the bcl-2 and mdm-2 genes, which are involved in the regulation of apoptosis, and the mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) gene, that functions as a regulator of various mitogen-activated protein kinase activities. The second phase, usually 5 h later, includes the induction of various stress proteins and ubiquitin, which are important in providing the chaperone mechanism and the turnover of damaged macromolecules. The third phase, which is 5-10 h later, includes the induction of genes that are apparently involved in reducing oxidative stress by metabolizing reactive oxygen species. In this phase, enzymes associated with tissue and cell remodeling are also elevated. These results demonstrate a complex gene expression array by bronchial epithelial cells in response to the insult of oxidants that are relevant to environmental pollutants.

Apoptosis↗

Lipoprotein-like particles and cholesteryl esters in human Bruch's membrane: initial characterization.

PURPOSE: To isolate and characterize cholesteryl ester-containing, lipoprotein-like particles (LLPs) from normal aged human Bruch's membrane (BrM)/choroid (Ch). METHODS: From BrM/Ch of 20 eyes of 10 donors aged >60 years, LLPs were released by high-salt buffer, fractionated by density gradient ultracentrifugation, and characterized by determining cholesterol, triglyceride, and phospholipid concentration (by enzymatic colorimetry and fluorometry); cholesteryl ester composition (by electrospray ionization mass spectrometry, ESI/MS); and particle morphology (by negative stain electron microscopy). Apolipoprotein (apo) gene expression was determined with RT-PCR, Western blot analysis, and immunofluorescence of retinal-choroidal cryosections. In paraformaldehyde-preserved eyes (20 eyes of 20 donors), cholesteryl ester composition of BrM/Ch, cornea, and sclera was determined by ESI/MS. RESULTS: A pooled fraction of LLP released from BrM/Ch (concentrated total LLP, density [d] < 1.24 g/mL fraction) was fractionated into two peaks. A large Peak 1 (with plasma LDL-HDL density range), containing predominantly phospholipid and unesterified cholesterol, was morphologically heterogeneous. A small Peak 2 (with plasma VLDL density range), enriched with esterified cholesterol, contained approximately 100 nm diameter round electron-lucent particles. Both peaks contained apoB and apoA-I, RPE and retina contained apoA-I mRNA transcripts, and BrM and drusen contained apoA-I immunoreactivity. Peaks 1 and 2, native RPE, and fresh BrM/Ch were cholesteryl linoleate enriched and contained little cholesteryl docosahexaenoate. Preserved BrM/Ch was cholesteryl oleate-enriched, unlike sclera and cornea. CONCLUSIONS: BrM/Ch LLP do not resemble plasma lipoproteins in density profile, cholesterol distribution, or morphology. Peak 2 contains EC-rich LLP resembling BrM particles in situ. BrM/Ch cholesteryl esters respond to long-term storage differently than esters of plasma lipoprotein origin accumulated in other ocular tissues. Evidence of intraocular apoB and apoA-I expression supports an emerging hypothesis that the RPE assembles and secretes a large, possibly novel, lipoprotein particle.

Apolipoprotein A-I↗

In situ staining for poly(ADP-ribose) polymerase activity using an NAD analogue.

Poly(ADP-ribose) polymerase (PARP) is a highly abundant nuclear enzyme which metabolizes NAD, in response to DNA strand breakage, to produce chains of poly(ADP-ribose) attached to nuclear proteins. PARP activation has been implicated in ischemia/reperfusion injury, but its biological significance is not fully understood. We have modified an existing in situ method for detection of PARP activity by using an NAD analogue in which adenine is modified by an "etheno" (vinyl) bridge. Etheno-NAD serves as a PARP substrate in an initial enzymatic reaction; a specific antibody to ethenoadenosine is then used in an immunohistochemical reaction to detect the production of modified poly(ADP-ribose). The method produces strong and specific labeling of nuclei in which PARP has been activated, i.e., those in which DNA strand breaks have been produced, and the results can be analyzed by microscopy, flow cytometry, or colorimetry. The method is applicable to cultured cells in several formats and to frozen tissue sections. The particular characteristics of the new method may assist in future in situ studies of PARP activation.

Animals↗

Radiotherapy for the treatment of pulmonary complications of paraquat poisoning.

The effect of radiotherapy on the pulmonary damage caused by paraquat (24% solution of 1,1'-dimethyl-4,4'-bipyridylium dichloride) was investigated in a preliminary series of nine patients. Paraquat intoxication was diagnosed by quantitative analysis of urine and plasma using colorimetry after extraction of a cation exchange column. The irradiation was given as a planned procedure from day 2 in cases 1 to 7, and after changes in chest X-ray were recognized in cases 8 and 9. A cobalt-60 unit with opposed anterior and posterior portals was used to give a total dose of 12.50 Gy (uncorrected) over 10 fractions, sparing the pericardium and mediastinum as much as possible. Each fraction consisted of 1.25 Gy (125 rad) given once a day, alternating between the left and right lungs. Radiological diagnosis consisted of clear chest X-rays (cases 2 to 4), pulmonary oedema (cases 7 and 9) and interstitial infiltrates (cases 1, 5, 6 and 8). Cases 1, 5 and 8 survived. Case 8 had residual interstitial infiltrates three months after ingestion but these had cleared one month later, suggesting that the diagnosis of irreversible fibrosis should only be made after a follow-up period of at least one year. The results have failed to show a definite benefit, but do support the fact that radiotherapy should be assessed carefully in a randomized trial which is now in progress.

Adolescent↗

Carotenoid content and flesh color of selected banana cultivars growing in Australia.

BACKGROUND: The problems of vitamin A deficiency and chronic diseases have emerged in recent years in some countries in the Micronesian region. These problems are associated with the dietary shift towards imported processed foods and lifestyle changes. Research in the Federated States of Micronesia indicates that yellow- and orange-fleshed banana cultivars contain significant levels of provitamin A carotenoids. OBJECTIVE: To identify further banana cultivars that may be promoted to alleviate vitamin A deficiency among children and women and chronic disease problems among adults. METHODS: Ripe fruit of banana cultivars growing in Australia (sourced mostly from a field research collection) were assessed for carotenoid content and flesh color. Ten cultivars with yellow or yellow/orange flesh color (including common cultivars of Southeast Asia and the Pacific Islands) were selected and compared with two cream-fleshed cultivars, including Williams, of the Cavendish group, the most commonly marketed banana worldwide. Carotenoid content was analyzed by high-performance liquid chromatography (HPLC). Flesh color was analyzed by HunterLab colorimetry. RESULTS: The yellow/orange-fleshed Asupina (a Fe'i banana) contained the highest level (1,412 microg/100 g) of trans beta-carotene, the most important provitamin A carotenoid, a level more than 20 times higher than that of Williams. All 10 yellow or yellow/orange-fleshed cultivars (Asupina, Kirkirnan, Pisang Raja, Horn Plantain, Pacific Plantain, Kluai Khai Bonng, Wain, Red Dacca, Lakatan, and Sucrier) had significant carotenoid levels, potentially meeting half or all of the estimated vitamin A requirements for a nonpregnant, nonlactating adult woman within normal consumption patterns. All were acceptable for taste and other attributes. The cream-fleshed cultivars had minimal carotenoid levels. There was a positive significant correlation between carotenoid content and deeper yellow/orange coloration indicators. CONCLUSIONS: These yellow- or yellow/orange-fleshed carotenoid-rich banana cultivars should be considered for promotion in order to alleviate vitamin A deficiency and chronic disease in susceptible target communities and to provide variety and enjoyment as exotic fruits in both developing and industrialized countries.

Antioxidants↗

Anti-proliferative effects, cell cycle G2/M phase arrest and blocking of chromosome segregation by probimane and MST-16 in human tumor cell lines.

BACKGROUND: Anticancer bisdioxopiperazines, including ICRF-154, razoxane (Raz, ICRF-159) and ICRF-193, are a family of anticancer agents developed in the UK, especially targeting metastases of neoplasms. Two other bisdioxopiperazine derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Cytotoxic activities and mechanisms of Raz (+)-steroisomer (ICRF-187, dexrazoxane), Pro and MST-16 against tumor cells were evaluated by MTT colorimetry, flow cytometry and karyotyping. RESULTS: Pro was cytotoxic to human tumor cell lines in vitro (IC50<50 microM for 48 h). Four human tumor cell lines (SCG-7901, K562, A549 and HL60) were susceptible to Pro at low inhibitory concentrations (IC50 values < 10 microM for 48 h). Although the IC50 against HeLa cell line of vincristine (VCR, 4.56 microM), doxorubicin (Dox, 1.12 microM) and 5-fluoruouracil (5-Fu, 0.232 microM) are lower than Pro (5.12 microM), ICRF-187 (129 microM) and MST-16 (26.4 microM), VCR, Dox and 5-Fu shows a low dose-related - high cytotoxic activity. Time-response studies showed that the cytotoxic effects of Pro are increased for 3 days in human tumor cells, whereas VCR, Dox and 5-Fu showed decreased cytotoxic action after 24 h. Cell cycle G2/M phase arrest and chromosome segregation blocking by Pro and MST-16 were noted. Although there was similar effects of Pro and MST-16 on chromosome segregation blocking action and cell cycle G2/M phase arrest at 1- 4 microM, cytotoxicity of Pro against tumor cells was higher than that of MST-16 in vitro by a factor of 3- 10 folds. Our data show that Pro may be more effective against lung cancer and leukemia while ICRF-187 and MST-16 shows similar IC50 values only against leukemia. CONCLUSION: It suggests that Pro has a wider spectrum of cytotoxic effects against human tumor cells than other bisdioxopiperazines, especially against solid tumors, and with a single cytotoxic pathway of Pro and MST-16 affecting chromosome segregation and leading also to cell G2/ M phase arrests, which finally reduces cell division rates. Pro may be more potent than MST-16 in cytotoxicity. High dose- and time- responses of Pro, when compared with VCR, 5-Fu and Dox, were seen that suggest a selectivity of Pro against tumor growth. Compounds of bisdioxopiperazines family may keep up their cytotoxic effects longer than many other anticancer drugs.

Antineoplastic Agents↗

Solvent effects in permeation assessed in vivo by skin surface biopsy.

BACKGROUND: Transdermal drug delivery has become an important means of drug administration. It presents numerous advantages but it is still limited by the small number of drugs with a suitable profile. The use of solvents that affect the skin barrier function is one of the classic strategies of penetration enhancement. Some of these solvents have well characterised actions on the stratum corneum, but the majority are still selected using empirical criteria. The objective of this work was to conduct a systematic study on the ability to affect skin permeation of solvents commonly used in transdermal formulations. An innovative methodology in this area was employed, consisting of the combination of skin surface biopsy with colorimetry. METHODS: The study compared in vivo differences in the permeation of a hydrophilic (methylene blue) and a lipophilic (Sudan III) dye, after treatment of the skin with different vehicles. Consecutive skin surface biopsies of each site were taken and the cumulative amounts of the dyes in the stripped stratum corneum were measured by reflectance colourimetry. RESULTS: Results indicate that the amount of methylene blue present in the stratum corneum varied significantly with different skin pre-treatments. Some solvents provided a 1.5 fold penetration enhancement but others decreased by almost half the permeation of the dye. The permeation of Sudan III was less significantly affected by solvent pre-treatment. CONCLUSIONS: This study has only superficially explored the potential of the combination of skin surface biopsy and colourimetry, but the encouraging results obtained confirm that the methodology can be extended to the study of more complex formulations.

Administration, Cutaneous↗

Positive end-expiratory pressure during KL4 surfactant instillation enhances intrapulmonary distribution in a simian model of respiratory distress syndrome.

Intrapulmonary distribution of a peptide-phospholipid (KL4) surfactant administered through an adapter permitting maintenance of positive end-expiratory pressure was compared with distribution by instillation with disconnection from mechanical ventilation in 10 surfactant-deficient Macaca mullata preterm infants. Animals received KL4 surfactant (200 mg/kg) when the arterial to alveolar (oxygen ratio) (a/Ao2) was < or = 0.22 (approximately 50 min after birth) on mechanical ventilation. Six rhesus infants received bolus instillation of two half doses of KL4 surfactant through an endotracheal tube adapter over 10-15 s while maintaining positive end-expiratory pressure (0.4 kPa) accompanied by turning to the right and left lateral positions for 60 s. In four rhesus premature infants KL4 surfactant was injected as two half-dose boluses through the endotracheal tube with disconnection from mechanical ventilation while positioning the infant rhesus monkey in the right and left lateral positions for 30 s of mechanical ventilation between instillation. Acute effects on oxygen saturation were monitored, and physiologic measures of a/Ao2, mean airway pressure, and the ventilatory efficiency index were monitored over the 12-h study. Intrapulmonary distribution of KL4 surfactant was determined using dye-labeled microspheres or [3H]dipalmitoylphosphatidylcholine-labeled surfactant, measured by colorimetry or by scintillation counting. Lungs of each monkey were processed into 50 +/- 5 pieces to determine distribution of radiolabel or microspheres and for scanning electron microscopy. The drop in oxygen saturation was greater among monkey infants disconnected from the ventilator for surfactant instillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗