Evidence that Oleic Acid Exists in a Separate Phase Within Stratum Corneum Lipids

Oleic acid is known to be a penetration enhancer for polar to moderately polar molecules. A mechanism related to lipid phase separation has been previously proposed by this laboratory to explain the increases in skin transport. In the studies presented here, Fourier transform infrared spectroscopy (FT-IR) was utilized to investigate whether or not oleic acid exists in a separate phase within stratum corneum (SC) lipids. Per-deuterated oleic acid was employed allowing the conformational phase behavior of the exogenously added fatty acid and the endogenous SC lipids to be monitored independently of each other. The results indicated that oleic acid exerts a significant effect on the SC lipids, lowering the lipid transition temperature (T _m) in addition to increasing the conformational freedom or flexibility of the endogenous lipid alkyl chains above their T _m. At temperatures lower than T _m, however, oleic acid did not significantly change the chain disorder of the SC lipids. Similar results were obtained with lipids isolated from the SC by chloroform:methanol extraction. Oleic acid, itself, was almost fully disordered at temperatures both above and below the endogenous lipid T _m in the intact SC and extracted lipid samples. This finding suggested that oleic acid does exist as a liquid within the SC lipids. The coexistence of fluid oleic acid and ordered SC lipids, at physiological temperatures, is consistent with the previously proposed phase-separation transport mechanism for enhanced diffusion. In this mechanism, the enhanced transport of polar molecules across the SC can be explained by the formation of permeable interfacial defects within the SC lipid bilayers which effectively decrease either the diffusional path length or the resistance, without necessarily invoking the formation of frank pores.     

Peripheral triacylglycerol extraction in the fasting and post-prandial states.

1. Triacylglycerol extraction by subcutaneous adipose tissue and forearm muscle was studied in nine normal subjects after an overnight fast and after the consumption of a mixed meal. 2. There was an inverse correlation between the total plasma fractional triacylglycerol extraction across the adipose tissue and the fasting arterial plasma triacylglycerol concentration. In contrast, there was no correlation between the lower fractional triacylglycerol extraction across the forearm muscle and the fasting plasma triacylglycerol concentration. 3. Chylomicron-triacylglycerol concentrations in arterial(ized) plasma increased post-prandially and peaked at 240-300 min. There was a comparable increase in the very-low-density lipoprotein-triacylglycerol concentration, peaking at 300 min. 4. Clearance of chylomicron-triacylglycerol by adipose tissue increased after the meal (P less than 0.05). In contrast, the clearance of very-low-density lipoprotein-triacylglycerol by adipose tissue decreased post-prandially (P less than 0.05). 5. Although there was significant uptake of chylomicron-triacylglycerol by the forearm muscle post-prandially, this was less than by the adipose tissue. Very-low-density lipoprotein-triacylglycerol was unaffected by passage through the forearm muscle at any time. 6. We conclude that the extraction of lipoprotein-triacylglycerol by human adipose tissue is important in determining the fasting plasma triacylglycerol concentration. Chylomicron-triacylglycerol, appearing in the plasma post-prandially, may compete with very-low-density lipoprotein-triacylglycerol for clearance by adipose tissue lipoprotein lipase, and this mechanism may explain, at least in part, the post-prandial rise in very-low-density lipoprotein-triacylglycerol. Forearm muscle, in contrast, appears to play a much smaller role in the extraction of plasma triacylglycerol, especially that in the very-low-density lipoprotein fraction.     

Nonpharmacological approaches for the treatment of urological chronic pelvic pain syndromes in men

Chronic nonbacterial prostatitis, or urological chronic pelvic pain syndrome (UCPPS), remains a common and often challenging disorder to evaluate and treat. Employing a more holistic approach, including urological therapy, physical therapy, and psychosocial perspectives, may be more appropriate for most patients. Growing evidence supports the use of biofeedback, myofascial trigger point release, prescribed exercise regimens, relaxation techniques, and supportive counseling to treat men with UCPPS.     

An update on the acquired immunodeficiency syndrome (AIDS)

The pandemic, acquired immunodeficiency syndrome (AIDS) has been described in 40 nations throughout the world. This paper describes the wide spectrum of gastrointestinal tract manifestations seen in this syndrome, with particular attention to the epidemiology, etiology, and measurement of these problems. Discussion of candidiasis, herpes simplex, “hairy” leukoplakia, Kaposi's sarcoma, cytomegalovirus, anal warts and carcinoma, chlamydial proctitis (LGV), coccidiosis, and mycobacterial diarrhea, as well as “gay bowel syndrome,” demonstrates the complex management problems associated with this condition.     

The medication of patients with oral lichen planus and the association of nonsteroidal anti-inflammatory drugs with erosive lesions

While the cause of lichen planus remains unclear, a number of drugs are known to produce oral and cutaneous lesions that clinically and histologically resemble lichen planus. In this study, the medication taken by 225 consecutive patients with oral lichen planus was compared with the drug histories of 202 age- and gender-matched control patients who were treated at the same clinics. Fifty-three percent of the patients with lichen planus and 44% of the control patients were taking one or more drugs (p greater than 0.05). However, 17% of the patients with lichen planus were taking nonsteroidal anti-inflammatory drugs (NSAID) compared with 9% of the control patients (p less than 0.05). There were no significant differences in the use of antihypertensive, oral hypoglycemic, or psychotropic drugs between the two groups. Almost 30% of the patients with the more severe erosive form of lichen planus were taking NSAID while fewer than 9% of the patients without erosions were taking this type of medication indicating a relationship between NSAID and the more severe form of lichen planus (p less than 0.01). Withdrawal from NSAID resulted in resolution or marked clinical improvement in the 12 patients tested. These results indicate that oral lichen planus may be aggravated or precipitated by NSAID and that withdrawal from the drug may benefit some patients.     

Elevated cholesterol levels. How to individualize treatment

Each of the three case studies represents a common presentation of a patient with elevated lipid levels. By categorizing patients using the guidelines of the National Cholesterol Education Program and considering the high-density lipoprotein cholesterol level, clinicians can more reliably assess response to treatment. An elevated total cholesterol level is only one of several important risk factors for coronary artery disease that must be confronted.     

DNA homologies shared among E. corrodens isolates and other corroding bacilli from the oral cavity

In a previous microbiological study of Eikenella corrodens, we noted the presence of E. corrodens strains with variability in colony morphology, as well as other corroding bacilli phenotypically similar to E. corrodens but which were unidentifiable on the basis of biochemical reactions. This raised questions as to whether E. corrodens constitutes a genetically heterogeneous group of organisms, and whether the unidentified corroding bacilli represent atypical E. corrodens or genetically unrelated organisms. In the present study, the genetic relationship among 14 E. corrodens isolates and 6 unidentified corroding bacilli was examined. DNA base compositions were determined from the melting temperatures of DNA samples. DNA homologies among E. corrodens and corroding bacilli were determined by DNA hybridization in solution using S1 nuclease. The % G + C content of E. corrodens strains varied from 56 to 58%, and from 56 to 60% for unidentified corroding bacilli. The DNA homologies among 12 E. corrodens isolates and 2 reference strains varied from 57 to 97%. Although these E. corrodens isolates exhibited variabilities in colony morphology and biochemical profile, no subspecies was identified. The unidentified corroding bacilli shared less than 33% homology with either of the E. corrodens reference strains. These corroding bacilli were further divided into 3 species on the basis of DNA hybridization studies using radiolabeled DNA from 2 representative corroding bacilli. One of the unidentified corroding bacilli appears to be a component of the normal flora in the human oral cavity. Our results indicate that E. corrodens is a genetically homogeneous species containing no recognizable subspecies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced activity in parathyroid hormone-(1-14) and -(1-11): novel peptides for probing ligand-receptor interactions.

The amino-terminal portion of PTH is critical for PTH-1 receptor (P1Rc) activation. In exploring this component of the ligand receptor interaction, we recently showed that the agonist potency of the weakly active PTH-(1-14)NH(2) peptide can be enhanced by natural amino acid substitutions at several positions, including position 11 (normally leucine). Here we show that the potency of PTH-(1-14)NH(2) can be enhanced by using nonnatural amino acids that increase the length and polarizability of the position 11 side-chain. Thus, in LLC-PK(1) cells stably expressing high levels of the human P1Rc, [homoarginine([Har)(11)]PTH-(1-14)NH(2) was 30-fold more potent for cAMP production than was native PTH-(1-14)NH(2). Combining the homoarginine-11 substitution with other recently identified activity-enhancing substitutions yielded [Ala(3,12),Gln(10),Har(11),Trp(14)]PTH-(1-14)NH(2), which was 1500-fold more potent than PTH-(1-14)NH(2) (EC(50) = 0.12 +/- 0.04 and 190 +/- 20 microM, respectively) and only 63-fold less potent than PTH-(1-34) (EC(50) = 1.9 +/- 0.5 nM). The even shorter analog [Ala(3),Gln(10),Har(11)]PTH-(1-11)NH(2) was also a full cAMP agonist (EC(50) = 3.1 +/- 1.5 microM). Receptor mutations at Phe(184) and Leu(187) located near the boundary of the amino-terminal domain and transmembrane domain-1 severely impaired responsiveness to the PTH-(1-11) analog. Overall, these studies demonstrate that PTH analogs of only 11 amino acids are sufficient for activation of the PTH-1 receptor through interaction with its juxtamembrane region.