Macrophage immunomodulation through new polymers that recapitulate functional effects of itaconate as a power house of innate immunity.

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. We developed a library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers resulted in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibited bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrated a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.

[Arthroscopic classification and management for the popliteal hiatus of the lateral meniscus tears].

OBJECTIVE: To bring forward an arthroscopic classification of the popliteal hiatus of the lateral meniscus (PHLM) tears and to assess the effects of arthroscopic all-inside repair with suture hook in management of such injuries. METHODS: This study involved 146 patients who underwent arthroscopic operation because of PHLM tears from April 2014 to October 2017, eliminating the patients who had discoid lateral meniscus. There were 81 males and 65 females, with 54 left knees and 92 right knees. The average ages were (34.7±3.7) years. Among the selected participants, there were 107 patients with anterior cruciate ligament (ACL) injuries, 39 patients with medial collateral ligament (MCL) injuries, and 48 patients with medial meniscus tears. The average preoperative Lysholm and International Knee Documentation Committee (IKDC) scores were 57.7±9.2 and 54.1±8.9, respectively. The arthroscopic classification was based on the extent and degree of PHLM tears and using the arthroscopic all-inside repair with suture hook for such injuries. For the patients associated with ACL injuries, the ipsilateral autograft hamstring tendons use as the reconstruction graft for single bundle ACL reconstructions. The suture anchors were used for treatment of MCL Ⅲ injuries, and the arthroscopic all-inside repair for medial meniscus tears. RESULTS: A total of 146 PHLM tears in 146 patients were divided into type Ⅰ (tears not involved in popliteus tendon incisura; n=86, 58.9%), type Ⅱ (tears involved in popliteomeniscal fascicles; n=36, 24.7%), and type Ⅲ (tears involved in popliteus tendon incisura; n=24, 16.4%). For type Ⅰ, there were three subtypes, including type Ⅰa: longitudinal tear (n=53, 61.6%), type Ⅰb: horizontal tear (n=27, 31.4%), and type Ⅰc: radial tear (n=6, 7.0%). For type Ⅱ, there were also three subtypes, including type Ⅱa: anterosuperior popliteomeniscal fascicle tear (n=5, 13.9%), type Ⅱb: posterosuperior popliteomeniscal fascicle tear (n=20, 55.6%), and type Ⅱc: both tears (n=11, 30.6%). For type Ⅲ, there were two subtypes, including type Ⅲa: horizontal tear (n=9, 37.5%), type Ⅲb: radial tear (n=15, 62.5%). In the follow-up for an average of 15.3±2.6 months, all the patients had done well with significantly improved Lysholm (84.6±14.3) and IKDC (83.2±12.8) scores at the end of the last follow-up relative to preoperative scores (P > 0.01). CONCLUSION: We propose that it is possible to classify lateral meniscus tears at the popliteal hiatus region for three types, which can summarize the injury characteristics of this area. The arthroscopic all-inside repair with suture hook for the PHLM tears can avoid stitching to popliteal tendon or narrowing popliteal hiatus and have satisfactory clinical results.

[Visual impact of sub-tenon's anesthesia during surgery for retinal detachment].

Objective: To investigate the visual impact and influence factors of sub-Tenon's anesthesia in retinal detachment patients during pars plana vitrectomy (PPV) or combined phacoemulsification and PPV surgery. Methods: In this prospective case series study, 104 consecutive patients who underwent PPV or combined phacoemulsification and PPV under sub-Tenon's anesthesia between October 2012 and December 2013 were enrolled. Intraoperatively, the patients were asked whether they could see the light of the operating microscope or not at 5 minutes after sub-Tenon's anesthesia, and at the end of phacoemulsification, core vitreous removal, peripheral vitreous removal and the whole surgery, with their contralateral eyes being covered tightly and no photobleaching. The best corrected visual acuity and visual evoked potentials were examined and compared with each other preoperatively and at 1.5 months and 3 months postoperatively. Chi-square test was used to compare the detection rate of amaurosis between different modus operandi and whether covered contra-lateral eye. Student-t test was used to compare the difference of age and preoperative BCVA between the patients with or without experienced amaurois. Lastly, BCVA between different times were tested by one-way ANOVA analysis. Results: Without covering the contralateral eyes, the incidence of no light perception in various surgical steps was 0%, while it was 72.1%(75/104), 93.8%(75/80), 96.2%(100/104), 96.2%(100/104) and 86.5%(90/104) at the five timepoints, respectively, when the contralateral eyes were covered tightly. The incidence was 51.9%(54/104), 85.0%(68/80), 85. 6%(89/104), 84.6%(69/104) and 66.3%(88/104), respectively, after photobleaching was excluded. Approximately 95.2%(99/104) of patients reported no light perception at least once, 54.5%(54/99) reported no light perception 5 minutes after sub-Tenon's anesthesia, and 30.3%(30/99) recovered light perception when the surgery was finished. All eyes recovered to at least light perception on the first postoperative day. The best corrected visual acuity and visual evoked potentials at 1.5 months and 3 months postoperatively were significantly better than those before surgery. The BCVA was 1.75±0.78 preoperative, 0.96±0.63 1.5 months after operation, and 0.92±0.57 3 months after operation. There was a significant statistical difference between preoperative BCVA and postoperative BCVA (F=50.61, P<0.01) . In patients without waveform detection preoperatively, PVEP waveform could be found in 43.6% and 61.4% of the pactients at 1.5 months and 3 months after operation respectively. In those had certain waveform preoperatively, PVEP amplitudes rise significantly after surgery (t(1.5)=-2.69, t(3)=-2.97, P<0.05) . Conclusions: No light perception was detected in various surgical steps of vitrectomy under sub-Tenon's anesthesia in most patients. The blocking of optic nerve conduction may be caused by sub-Tenon' s anesthesia. Photobleaching can also have some effect. The incidence of no light perception during the surgery was not correlated with preoperative visual acuity, age and gender. Moreover, the effect was transient and harmless to visual function.(Chin J Ophthalmol, 2017, 53: 332-337).

Clinical imaging findings in a girl with Hutchinson-Gilford progeria syndrome.

We report an 82-year-old girl with premature aging, a karyotype of 46,XX and a de novo c.1824C>T mutation encoding p.G608G in the lamin A gene. The clinical features of accelerated aging and the molecular finding were consistent with the diagnosis of Hutchinson-Gilford progeria syndrome (HGPS). In this presentation, we demonstrate the radiological imaging findings of skeletal, oral and craniofacial phenotypes of abnormalities associated with HGPS. The oral and craniofacial abnormalities caused dental caries, severe malocclusion, and swallowing, feeding and speech problems. Dural calcification, and granulation in the ear drum and external ear canal were additionally observed.

Еffеct оf cоupling thе TiО2 аnd WО3 lоаdеd with nоblе mеtаls fоr UV phоtоdеgrаdаtiоn оf оxаliс асid, аssistеd bу оzоnе.

Nоblе mеtаls suppоrtеd оn TiО2 (Dеgussа P25) mоdifiеd with WО3 undеr thе еffесt оf fееding оxуgеn аnd оzоnе соntаining mixturе tо thе rеасtоr undеr UV-С irrаdiаtiоn wеrе еxаminеd fоr thеir саtаlуtiс асtivitу in thеrеасtiоn оf оxаliс асid liquid phаsе оxidаtiоn. Thе sаmplеs wеrе sуnthеsizеd bу еxtrасtivе-pуrоlуtiс mеthоd bу lоаding 4 wt.% WО3 аnd 1 wt.% оf thе асtivе mеtаl hаving pаrtiсlеs sizе vаrуing frоm 5 tо 30 nm. Thе XPS, XRD, TЕM аnd BЕT mеthоds wеrе еmplоуеd fоr thеir struсturаl аnd сhеmiсаl сhаrасtеrizаtiоn. In thе prеsеnсе оf оxуgеn undеr UV light thе limiting stеp zеrо-оrdеr rеасtiоn rаtе оf TiО2/WО3/Pt sаmplе wаs highеst аmоng thе tеstеd саtаlуsts аnd it wаs 2.3 timеs highеr thаn thаt оf thе purе TiО2 undеr thе sаmе соnditiоns. Thе inсrеаsеd асtivitу оf thе соmpоsitе саtаlуsts wаs duе tо thе mоrе еffiсiеnt sеpаrаtiоn оf thе еlесtrоn-hоlе сhаrgе саrriеrs gеnеrаtеd during irrаdiаtiоn, whiсh wаs соmbinаtiоn frоm thе bеnеfiсiаl еffесt оf thе WО3 аnd nоblе mеtаl. Furthеr, thе еffесtivеnеss оf thе саtаlуsts in rеgаrd tо thе phоtооxidаtiоn оf оxаliс асid in thе prеsеnсе оf оzоnе is grеаtеr bеtwееn 4-5 timеs fоr аll tеstеd sаmplеs. Thе highеst асtivitу undеr fееding оf оzоnе wаs shоwn bу TiО2/WО3/Pd thаt wаs аsсribеd tо thе highеst оzоnе dесоmpоsitiоn аbilitу оf thе pаllаdium suppоrtеd оn TiО2 rеsulting in асtivе оxуgеn аtоms fоrmаtiоn thаt fасilitаtе thе dеgrаdаtiоn оf оxаliс асid.

Large quantum-spin-Hall gap in single-layer 1T' WSe2.

Two-dimensional (2D) topological insulators (TIs) are promising platforms for low-dissipation spintronic devices based on the quantum-spin-Hall (QSH) effect, but experimental realization of such systems with a large band gap suitable for room-temperature applications has proven difficult. Here, we report the successful growth on bilayer graphene of a quasi-freestanding WSe2 single layer with the 1T' structure that does not exist in the bulk form of WSe2. Using angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy/spectroscopy (STM/STS), we observe a gap of 129 meV in the 1T' layer and an in-gap edge state located near the layer boundary. The system's 2D TI characters are confirmed by first-principles calculations. The observed gap diminishes with doping by Rb adsorption, ultimately leading to an insulator-semimetal transition. The discovery of this large-gap 2D TI with a tunable band gap opens up opportunities for developing advanced nanoscale systems and quantum devices.

The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans.

The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly related to the amount of cholesterol in the test meal, and absorption was not affected by background diets high or low in cholesterol content.

Cholesterol metabolism and placental transfer in the pregnant Rhesus monkey.

The placental transfer of cholesterol (5-cholesten-3beta-ol) was investigated by giving pregnant rhesus monkeys cholesterol-1alpha-(3)H or cholesterol-4-(14)C and then determining the cholesterol specific activity (SA) in maternal serum and in fetal serum and tissues. An isotopic steady state was established in five pregnant animals by the daily feeding of a tracer dose of cholesterol-4-(14)C. Comparison of maternal and fetal serum cholesterol SA revealed that an average of 42.6% of the serum cholesterol in the term fetus originated by transfer from the maternal blood. The remainder presumably arose by fetal synthesis de novo. Fetal tissues had cholesterol SA equal to or slightly less than that of fetal serum, except for brain which had a SA only 5% that of fetal serum. In other studies a single intravenous dose of radioactive cholesterol was given to either mother or fetus in late pregnancy. The time for detectable passage across the placenta in either direction was between 4 and 24 hr. With maternal administration of the isotope, there was equilibration of maternal and fetal serum cholesterol SA after 10-12 days. With fetal injection of isotopic cholesterol, however, the maternal cholesterol SA never attained a level more than 5% of fetal SA. This indicated that the net cholesterol flux was strongly in the direction of mother to fetus. Serum cholesterol levels were significantly greater in maternal than in fetal serum (80.3+/-18.5 vs. 59.6+/-15.6 mg/100 ml). Maternal serum cholesterol concentration in the monkey was significantly lower in late pregnancy than during the puerperium. Studies of breast milk indicated that approximately two-thirds of milk cholesterol was transferred from the maternal blood.

Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis.

Sitosterolemia and xanthomatosis together are a disease characterized by premature cardiovascular disease, and by elevated plasma concentrations of total sterols and of plant sterols, especially sitosterol which is hyperabsorbed. In order to determine whether this abnormal metabolism also involved other sterols, a patient with sitosterolemia was fed a diet high in shellfish that contain significant quantities of noncholesterol sterols, some of which are less well absorbed than cholesterol in humans. Compared with control subjects (n = 8), the sitosterolemic subject had an increased absorption of 22-dehydrocholesterol (71.5% vs. 43.8 +/- 11.4%, mean +/- SD), C-26 sterol (80.6% vs. 49.3 +/- 11.4%), brassicasterol (51.8% vs. 4.8 +/- 4.2%), and 24-methylene cholesterol (60.5% vs. 16.0 +/- 8.3%). This enhanced absorption was associated with an increased plasma total shellfish sterol level (13.1 mg/dl vs. 1.9 +/- 0.7 mg/dl in normals). In the sitosterolemic subject, as in normals, the shellfish sterols were not preferentially concentrated in any lipoprotein class, and 50-65% of these sterols were in the esterified form in plasma. Bile acids and neutral sterols were quantitated in bile obtained by duodenal aspiration. The bile acid composition did not differ significantly in the sitosterolemic subject compared with the normal controls. The sitosterolemic subject, though, was unable to concentrate normally the neutral shellfish sterols in bile. The normal controls concentrated the shellfish sterols in bile 6.3 +/- 1.7-fold relative to the plasma shellfish sterol concentration whereas the study subject was only able to concentrate them 2.1-fold. We propose that sitosterolemia and xanthomatosis occur from a generalized abnormality in the usual ability of the gut mucosa and other tissues of the body to discriminate among many different sterols. This has important implications for the understanding of the pathophysiology of this disease and for therapeutic recommendations.

The interaction of dietary fibers and cholesterol upon the plasma lipids and lipoproteins, sterol balance, and bowel function in human subjects.

To identify any metabolic effects of dietary fiber upon cholesterol metabolism in man, six adult volunteer subjects were fed eucaloric cholesterol-free formula diets, with and without added dietary fiber for two 4-wk periods. A large quantity of dietary fiber was fed, some 60 g of plant cell wall material (or 16 g of crude fiber) derived from corn, beans, bran, pectin, and purified cellulose. This provided about five times the fiber intake of the typical American diet. The addition of fiber to the cholesterol-free diet did not change either the plasma cholesterol level (171+/-21 mg/dl, SEM, to 167+/-18) or the triglyceride (103+/-39 to 93+/-27 mg/dl). The excretion of both endogenous neutral steroids and bile acids were unchanged with fiber (505+/-41 to 636+/-75 mg/day and 194+/-23 to 266+/-47 mg/day, respectively.) However, total fecal steroid excretion was increased 699+/-29 to 902+/-64 mg/day, P < 0.025). With fiber, intestinal transit time was decreased (59+/-9 to 35+/-8 h, P < 0.005), and both the wet and dry stool weights were greatly increased.A second group of six subjects was fed similar diets containing 1,000 mg cholesterol derived from egg yolk. The addition of fiber to the 1,000-mg cholesterol diet did not alter either plasma cholesterol level (233+/-26 to 223+/-36 mg/dl) or triglyceride (102+/-19 to 83+/-11 mg/dl). The excretion of endogenous neutral steroids (618+/-84 to 571+/-59 mg/day), of bile acids (423+/-122 to 401+/-89 mg/day), and of total fecal steroids (1,041+/-175 to 972+/-111 mg/day) were unchanged by fiber. The absorption of dietary cholesterol was not altered when fiber was added to the 1,000-mg cholesterol diet (44.0+/-3.3 to 42.9+/-2.5%). A two-way analysis of variance utilizing both groups of subjects indicated a significant (P < 0.001) effect of dietary cholesterol upon the plasma cholesterol concentration. We concluded that a large quantity of dietary fiber from diverse sources had little or no effect upon the plasma lipids and sterol balance in man in spite of the fact that intestinal transit time and stool bulk changed greatly.

Cholesterol and bile acid balance in Macaca fascicularis. Effects of alfalfa saponins.

We determine the effects of alfalfa top saponins on cholesterol and bile acid balance in eight cynomolgus macaques (Macaca fascicularis). The monkeys ate semipurified food containing cholesterol with or without added saponins. The saponins decreased cholesterolemia without changing the levels of high density lipoprotein-cholesterol; hence, they reduced the total cholesterol/high density lipoprotein-cholesterol ratio. Furthermore, they decreased intestinal absorption of cholesterol, increased fecal excretion of endogenous and exogenous neutral steroids and bile acids, and decreased the percent distribution of fecal deoxycholic and lithocholic acids. The fecal excretion of fat was also slightly increased, but steatorrhea did not occur. We saw no signs of toxicity in the monkeys after 6 or 8 wk of saponin ingestion. The data suggest that alfalfa top saponins may be of use in the treatment of patients with hypercholesterolemia, but long-term studies on possible toxicity are needed before this therapy can be recommended for humans.

[Effects and related mechanism of bivalirudin on the survival of random skin flap on the back of rat].

Objective: To investigate the effects and related mechanism of bivalirudin on the survival of random skin flap on the back of rat. Methods: Thirty SD rats were divided into bivalirudin group and normal saline group according to the random number table, with 15 rats in each group. The random flap model with size of 9 cm×3 cm was reproduced on the back of rats in two groups. Immediately post injury, rats in bivalirudin group were intraperitoneally injected with 5 mg/mL bivalirudin (0.8 mL/kg), while rats in normal saline group were intraperitoneally injected with normal saline (0.8 mL/kg) once a day. The continuous injection lasted for 7 days. The flap was divided into distal area, middle area and proximal area averagely based on the flap blood supply. On post injury day (PID) 1, 3, and 7, the overall survival of each area of flap was observed with naked eyes. On PID 7, the survival rate of flap was calculated, and then the morphology of skin tissue at the center of the three areas of flap was observed by HE staining, the microvessel density (MVD) of the middle area of flap was calculated, and the expression of vascular endothelial growth factor (VEGF) of the middle area of flap was detected with immunohistochemical staining. Data were processed with t test. Results: (1) On PID 1, flaps of rats in two groups had different degrees of swelling, mainly concentrated in distal area, but there was no obvious necrosis. The middle area and proximal area of flaps in two groups were survived. On PID 3, the necrosis of flaps of rats in two groups was concentrated in the middle area, while the proximal area of flap was still in survival state, and most distal area of flap was necrosis with a little scab. On PID 7, the necrosis of middle area of flaps of rats in two groups was gradually fused, and the survival area of flap of rats in bivalirudin group was larger than that in normal saline group. The distal area of flap was almost necrotic, and the proximal area of flap was almost survived. (2) On PID 7, the survival rate of flap of rats in bivalirudin group was (64±4)%, significantly higher than that in normal saline group [(45±3)%, t=13.49, P<0.01]. (3) On PID 7, the histological morphology of distal area of flap of rats in two groups was similar, the inflammatory cells were infiltrated abundantly, and tissue edema was obvious. A large number of new blood vessels appeared in the middle area of flap of rats in bivalirudin group, with the formation of collateral vessels, and basic dilation of new blood vessels was seen. There were fewer new blood vessels appeared in the middle area of flap of rats in normal saline group, and dilation of new blood vessels was not obvious. There was little inflammatory cells infiltration in the proximal area of flap of rats in two groups. Compared with that in normal saline group, tissue edema extent of proximal area of flap of rats in bivalirudin group was less, and expansion was observed in more blood vessels. (4) The MVD of middle area of flap of rats in bivalirudin group was (26±5)/mm(2,) significantly higher than that in normal saline group [(18±3)/mm(2,) t=5.43, P<0.05]. (5) The expression of VEGF of middle area of flap of rats in bivalirudin group was 6 534±384, significantly higher than that in normal saline group (4 659±448, t=12.31, P<0.05). Conclusions: Bivalirudin can promote the survival of random skin flap in rats, and the mechanisms may include reducing the formation of thrombosis, improving the blood supply of flap, and increasing the expression of VEGF, promoting the formation of new blood vessels.

The origin of plant sterols in the skin surface lipids in humans: from diet to plasma to skin.

To test the hypothesis that plant sterols found in the skin surface lipids of humans originated from diet after their absorption from intestine into plasma and then transferred to skin, we studied the 24-h excretion of plant sterols and cholesterol from skin and in feces in a hyperlipoproteinemic (type IIa) patient fed formula diets providing varying quantities of plant sterols (0-30 g/day) and cholesterol (0-1000 g/day). Upon feeding a sterol-free diet, the beta-sitosterol excretion from the skin decreased progressively, from about 6 mg/day to 0.08 mg/day by 83 days and then completely disappeared. With addition of plant sterols (about 30 g/day) to the diet, beta-sitosterol reappeared in the skin surface lipids and rose to nearly 5 mg/day by 6 weeks. With feeding of the sterol-free diet, the fecal excretion of beta-sitosterol and the 2 other plant sterols decreased gradually and by week 4 disappeared completely from the feces and continued to be absent from the feces as long as the diet was free of plant sterols. The results demonstrated clearly that plant sterols which were absorbed into the plasma from the diet were excreted into the skin surface lipids after being transferred from the plasma to the skin.

Biochemical markers for puberty in the monkey testis: desmosterol and docosahexaenoic acid.

We previously reported that the sperm of rhesus monkeys and humans uniquely contain large amounts of desmosterol not found in other tissues and have a high concentration of the highly polyunsaturated n-3 fatty acid, docosahexaenoic acid (22:6 n-3). However, the lipid composition of the testis, from which sperm originate, is unknown. During puberty, the testis undergoes remarkable morphological changes as testosterone levels rise and sperm production begins. We hypothesized that testicular maturation might also involve dramatic changes in lipid composition. Accordingly, we characterized the sterol and fatty acid composition of the testis of rhesus monkeys throughout the lifespan, from birth to old age. Although the cholesterol content in the testis remained relatively unchanged throughout life, the desmosterol content first decreased from 59 microg/g in infants to 6 microg/g in prepubertal monkeys, increased to 83 microg/g during puberty, and reached a plateau of 248 microg/g in the young adult, where it remained into old age. The polyunsaturated fatty acid composition of the testis also changed markedly. Docosahexaenoic acid (22:6 n-3) increased from 5.1% of total fatty acids in infants and juveniles to 18.1% in postpubertal young adults. Although some n-6 fatty acids, arachidonic (20:4 n-6) and linoleic (18:2 n-6), decreased from 16.0% and 10.0% in prepubertal juveniles, respectively, to 7.1% and 3.3% in young adults; dihomogamma-linolenic acid (20:3 n-6), the precursor of 1 series PGs, increased greatly from 1.8% to 10.3%. Similar changes occurred in both membrane and storage lipids (phospholipids and triglycerides), respectively. After puberty, the testicular fatty acid pattern remained stable into old age. Our data demonstrated that puberty is accompanied by substantial changes in the lipid composition of the primate testis. These changes suggest that desmosterol and both n-3 and n-6 polyunsaturated fatty acids may have important roles in sexual maturation.

Are the n-3 fatty acids from dietary fish oil deposited in the triglyceride stores of adipose tissue?

Adipose tissue is the chief reservoir of the essential fatty acids (n-3 and n-6). To study the incorporation of the dietary n-3 fatty acids eicosapentaenoic acid (EPA) (20:5) and docosahexaenoic acid (DHA) (22:6), and a unique monounsaturated fatty acid, cetoleic acid (22:1n-11), into adipose tissue, rabbits were fed two different processed fish oils: MaxEPA (high in EPA and DHA; Seven Sea Ltd, Hull, UK) and herring oil (high in cetoleic acid). EPA and DHA increased from 0% of total adipose tissue fatty acid, in the adipose tissue of control rabbits to 2.2% and 4.9%, respectively, in MaxEPA-fed rabbits. The DHA-to-EPA ratio in the adipose tissue was higher than that in the diet, indicating alternative metabolic pathways for EPA. In the adipose tissue of herring-oil-fed rabbits, cetoleic acid increased from 0% to 7.9% of total fatty acids. The deposition of EPA and DHA was 1.8% and 2.8%, respectively. Our data indicated that these unique long-chain unsaturated fatty acids from dietary fish oils were readily incorporated into the fat stores from whence they could be mobilized.

Fecal steroids of the coprolite of a Greenland Eskimo mummy, AD 1475: a clue to dietary sterol intake.

BACKGROUND: Sterols in feces reflect sterols in the diet. In previous analyses of the fecal steroids in 1000-2000-y-old Native American coprolites found in the dry caves of Nevada, we showed that the sterol nucleus was stable. The coprolites provided useful dietary information. OBJECTIVE: In the present study, we analyzed the fecal steroids of an Eskimo mummy buried and frozen >500 y ago in Greenland. We compared these analyses with our findings in the coprolites from Nevada and in present-day stool samples from Tarahumara Indians of Mexico and Americans consuming low- and high-cholesterol diets. DESIGN: The fecal material from the Eskimo mummy was subjected to saponification, extraction, and digitonin precipitation. The sterols and bile acids were further analyzed by thin-layer chromatography and gas-liquid chromatography. RESULTS: The fecal steroids of the Greenland Eskimo mummy were remarkably similar to those of present-day stool samples. However, unlike in the stool of modern humans, a portion of the neutral steroids in the coprolite had been converted to sterol epimers. Instead of deoxycholic acid, 3alpha,6beta,12alpha-trihydroxycholanic acid was one of the major fecal bile acids. The plant sterol output in the coprolite was only 0.4% of the output of Americans consuming 250-400 mg plant sterols/d. The ratio of bile acid to cholesterol in the coprolite was similar to that in stool from Tarahumara Indians consuming a low-cholesterol diet. CONCLUSION: The sterol nucleus is stable when frozen. The analysis of coprolite showed that the young Eskimo woman had consumed a diet very low in plant sterols and moderate to low in cholesterol content.

Are dietary saturated, monounsaturated, and polyunsaturated fatty acids deposited to the same extent in adipose tissue of rabbits?

The objective of this study was to determine the effect that different dietary fatty acids would have on the fatty acid composition of adipose tissue. Thirty adult rabbits were starved 3-4 wk to deplete adipose tissue stores. They were then refed five different fats (linseed, rapeseed, cocoa butter, palm, and safflower oils) to regain initial body weights. The fatty acids of the adipose tissue, in general, reflected the diet. Positive correlations between the amount of the five commonly consumed fatty acids (palmitic, stearic, oleic, linoleic, and linolenic acids) in the diet and their deposition into the adipose tissue were observed. All polyunsaturated and monounsaturated fatty acids were well incorporated into the adipose tissue, even linolenic acid. The deposition of dietary saturated fatty acids (ie stearic acid) was limited. Our data showed that the fatty acids of dietary fats may greatly affect adipose fatty acid composition. Thus, adipose stores of essential fatty acids can be greatly augmented by diet.

Lymphatic absorption of shellfish sterols and their effects on cholesterol absorption.

Studies have been conducted on the absorbability of individual sterols from a mixture of oyster sterols when administered intragastrically to rats with indwelling catheters in the left thoracic duct. In addition, the effect of oyster sterols on cholesterol absorption has been assessed using [4-14C] cholesterol in the mixture, and comparison against absorption of cholesterol alone. The order of absorbability (percentage absorption) of individual sterols from the mixture of oyster sterols was: cholesterol greater than or equal to 26-carbon sterols greater than or equal to dehydrocholesterol greater than 24-methylene cholesterol greater than brassicasterol greater than plant sterols. The absorption of noncholesterol sterols was 8.2 +/- 0.8% of the fed dose, or less than half of that for an equivalent level of cholesterol alone. The presence of these sterols in mixtures containing cholesterol reduced lymphatic absorption of cholesterol by 25 to 40% compared to absorption of the same amount of cholesterol administered alone, or to an amount of cholesterol equal to the total oyster sterols, respectively. These studies suggest that shellfish sterols are poorly absorbed, and, like plant sterols, effectively reduce dietary and/or endogenous cholesterol absorption from the intestine.

Comparative lymphatic absorption of sitosterol, stigmasterol, and fucosterol and differential inhibition of cholesterol absorption.

Studies have been conducted on the lymphatic absorption of sitosterol (24 alpha-ethyl cholesterol), stigmasterol (delta 22, 24 alpha-ethyl cholesterol), and fucosterol (24-ethylidine cholesterol) when administered intragastrically to rats. In addition, the effect of each sterol on absorption of endogenous cholesterol has been assessed by including tracer cholesterol in the administered test emulsion. Analysis of 24-h lymph collections by GLC-mass spectrometry demonstrated that all three sterols were poorly absorbed to the extent of only 3 to 4% of the administered dose of 50 mg. In contrast, cholesterol absorption under similar conditions was about 42% of the administered dose. Administration of either sitosterol or stigmasterol resulted in an equally effective inhibition of cholesterol absorption (54%). Under identical conditions fucosterol had no effect on absorption of luminal cholesterol. The data suggest that the mechanism(s) for intestinal discrimination of sterols for absorption may be independent of the mechanism for interference with efficient cholesterol uptake by the intestine.

The absorption of cholesterol and the sterol balance in the Tarahumara Indians of Mexico fed cholesterol-free and high cholesterol diets.

The Tarahumara Indians of Mexico are habituated to a very low cholesterol, low fat diet and have lifelong low plasma cholesterol concentrations. To study cholesterol metabolism in these unusual people, 8 Tarahumara men were fed sequentially a cholesterol-free diet and then a diet containing 900 mg cholesterol under controlled conditions. The intestinal absorption of cholesterol, fecal steroid excretion and sterol balance were determined. During the high cholesterol diet period, the plasma cholesterol level increased from 113 +/- 8 mg/dl to 147 +/- 11 mg/dl (means +/- SD). Cholesterol biosynthesis decreased from 14.0 +/- 0.7 to 7.1 +/- 1.0 mg/kg/day (means +/- SE). The intestinal absorption of cholesterol was 27.7 +/- 6.7% (means +/- SE) during both dietary periods. Compared to other cultures, Tarahumaras had a reduced ability to absorb dietary cholesterol and higher total sterol turnover primarily because of an increased bile acid output. The total sterol disposition over three weeks of the high cholesterol diet accounted for all the absorbed dietary cholesterol.