Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Protection of photosensitized rats against long ultraviolet radiation by topical application of compounds with structures similar to that of dihydroxyacetone

Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320-400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation.     

Xylose disposition in humans as a function of age

D-xylose disposition was examined in 24 healthy men between 32 and 85 years of age. Xylose was administered as a 5 gm iv infusion and as a 25 gm po solution. Serum xylose concentrations and urinary excretion of intact xylose were determined. There were statistically significant inverse relationships with age for each of the following parameters after intravenous infusion: elimination rate constant (r2 = 0.71); systemic clearance (r2 = 0.66); renal clearance (r2 = 0.66); and nonrenal clearance (r2 = 0.35). Similar inverse relationships were found after oral dosing for the elimination rate constant (r2 = 0.69) and renal clearance (r2 = 0.54). There was no significant age relationship for the apparent volume of distribution or the steady-state volume of distribution. The percentage of the oral and intravenous dose recovered in urine up to 5 hours after dosing was significantly and inversely correlated with age. The implications of the latter finding are discussed with regard to the interpretation of the xylose tolerance test used to assess gastrointestinal absorptive capacity.     

Familial achalasia associated with adrenocortical insufficiency, alacrima, and neurological abnormalities

We report on two brothers with achalasia, adrenocortical insufficiency, alacrima, short stature, microcephaly, ataxia, optic atrophy, and developmental delay. The parents and three sibs are unaffected. Achalasia, adrenocortical insufficiency, and alacrima comprise a recently characterized familial multisystem disorder of unknown cause. Achalasia has also been described in association with microcephaly and mental retardation in one family and ataxia, optic atrophy, and mental retardation in another. The above reports and these sibs may represent variants of a single pleiotropic recessive gene. We suggest that abnormalities of the central nervous system are a manifestation of the achalasia, adrenocortical insufficiency, alacrima syndrome.     

The pH Optima for Papain and Bromelain Treatment of Red Cells

The action of papain and bromelain, prepared over a pH range from 4.6 to 8.6, was evaluated for the ability to render red cells agglutinable by five incomplete antibodies of differing blood group specificities using a two-stage technique. The optimal pH for treatment of red cells by activated papain or bromelain was between 5.4 and 5.8. Above this pH range, a fall in serological sensitivity was apparent which was much more pronounced with papain than with bromelain. The optimal pH for enzyme treatment of red cells can be achieved in two-stage techniques, but not in one-stage techniques due to the buffering effect of serum proteins.     

P2X(7) receptors are expressed during mouse nephrogenesis and in collecting duct cysts of the cpk/cpk mouse.

BACKGROUND: Purinergic receptors are cell-surface molecules that bind extracellular nucleotides, notably ATP. The P2X family includes seven nonselective ion channels with one member, P2X(7), implicated in cytolytic pore formation and cell death. MATERIALS AND METHODS: We sought P2X(7) expression in mouse nephrogenesis and cpk/cpk renal cyst growth, conditions in which both proliferation and apoptosis are prominent. RESULTS: P2X(7) immunolocalized to condensed metanephric mesenchyme: both proliferation and apoptosis were detected in this compartment, assessed by proliferating cell nuclear antigen expression and propidium iodide-stained pyknotic nuclei respectively. Later in nephrogenesis, P2X(7) was detected in collecting ducts, a pattern persisting to maturity. A mesenchymal to epithelial shift of P2X(7) expression was also documented in ureter development. In cpk/cpk kidneys, P2X(7)-expressing collecting duct cysts dominated histology from two weeks until four weeks after birth, when animals die from uremia. In polycystic kidneys pyknotic nuclei were rarely identified in P2X(7)-expressing epithelia, but were detected between cysts, consistent with a non-apoptotic role for P2X(7) in cyst enlargement. CONCLUSION: P2X(7) is expressed during normal nephrogenesis and in a model of congenital polycystic kidney disease. Further experiments are necessary to define possible functions of P2X(7) in these settings.     

Intrapartum fetal heart rate patterns and neonatal intraventricular hemorrhage

A goal for the obstetrician and neonatologist is to screen for risk factors associated with intraventricular hemorrhage (IVH) in the low-birthweight infant. Perinatal events that lead to neonatal metabolic and cardiovascular derangements seem to provoke IVH, and conflicting reports have implicated labor as being contributory. A fetal heart rate (FHR) abnormality during premature labor may be a predictor of subsequent neonatal IVH. For this reason, 5 years of FHR tracings at two university medical centers were reviewed for inborn infants who were delivered after premature labor and weighed less than or equal to 2000 gm. Sixty-four infants developed IVH, but pre-existing labor with a discernible FHR pattern was recorded in only 38 (59%) cases. Interpretations were reassuring in 17 (45%) cases, suspicious in 7 (18%) cases, and ominous in 14 (37%) cases. This proportion of FHR patterns was not significantly different from a matched group of premature infants without IVH during the same period. Interpretations of intrapartum FHR patterns of low-birthweight infants are limited, especially before 30 weeks gestation, and not useful in predicting neonatal IVH.     

Adjuvant radiotherapy in carcinomas of the uterine cervix: the prognostic value of hemoglobin levels

Anemia has been associated with a poorer treatment response and reduced survival in women undergoing primary radiotherapy (RT) or radiochemotherapy for advanced cervical carcinoma. This study aimed to determine the influence of anemia on outcome in patients with cervical carcinoma undergoing adjuvant RT. Medical records were reviewed for 183 cervical cancer patients who had received adjuvant RT because of risk factors after radical surgery (n= 109) or inadequate primary surgery (simple hysterectomy; n= 74). Kaplan-Meier and Cox regression analyses were used to study hemoglobin levels before and during adjuvant RT in relation to recurrence-free and overall survival. Hemoglobin values > or =11 g/dL were considered normal, while those <11 g/dL indicated anemia. Hemoglobin levels before RT influenced significantly overall survival and recurrence-free survival across the whole group (overall survival--log rank(all patients)= 7.5; df = 1; P= 0.006). However, subgroup analysis showed that the observed difference was mainly due to the group of women who had undergone inadequate primary surgery (overall survival--log rank(inadequate surgery)= 10.8; df = 1; P= 0.001). Multifactorial regression analyses comparing hemoglobin before RT with grading and tumor stage confirmed the prognostic value of hemoglobin values. Maintaining normal hemoglobin values before and during adjuvant RT seems to be important, especially in patients who have had inappropriate simple hysterectomy, which may resemble a therapeutic situation.