Association Between the Fertile Period and Live Birth Post-Kidney Transplantation: A Retrospective Single-Center Cohort Study.

BACKGROUND: Despite restoration of fertility after kidney transplantation, the benefit is limited in female kidney recipients. Our objective is to determine the reasons for this discrepancy. METHODS: We evaluated 315 women who underwent kidney transplantation from 1983 to 2015 (a median of age at transplantation [10th-90th percentile] of 32 years [7-55 years]); 230 recipients between the ages of 15 to 49 years old as of March 2016 were observed. RESULTS: We experienced 10 abortions and 21 live births from our 23 recipients and 2 abortions and 7 live births in 7 recipients from other transplant center. The live birth rate was 8.9 per 1000 female transplant recipients of childbearing age. Seven recipients received either treatments of artificial insemination or in vitro fertilization. Average age at pregnancy was 33.2 ± 3.2 years old, and the fertile period post-transplantation was longer in recipients with live births than those without live births (14.1 ± 7.1 vs 9.9 ± 7.3 years, P < .05). In 42.9% of recipients with live birth, pregnancy-induced hypertension was observed in the last trimester. The gestational age and the average birth weight were 32.8 ± 5.0 months and 2184 ± 632 g, respectively. During follow-up of 14.5 years, there was one case of graft loss, which is a rate of 2.5 per 1000 female recipients. CONCLUSION: Although pregnancy complications are often observed in kidney recipients, graft survival is less influenced by pregnancy. Importantly, kidney disease at childbearing age disrupts pregnancy even after kidney transplantation.

Pharmacokinetic Profile of Twice- and Once-daily Tacrolimus in Pediatric Kidney Transplant Recipients.

BACKGROUND: The aim of this study was to assess the differences in pharmacokinetic (PK) profiles after the 1:1 ratio-based conversion from a twice-daily to a once-daily tacrolimus formulation (TD-TAC and OD-TAC, respectively) in pediatric recipients of kidney transplants. METHODS: TD-TAC was initially administered to 29 pediatric patients who underwent kidney transplantations between April 2010 and September 2015 and were then subsequently switched to OD-TAC. The switch dose ratio was 1:1, and the 24-hour complete PK parameter assessment was performed before and after the regimen was changed from TD-TAC to OD-TAC. RESULTS: The mean total daily dose at baseline was 5.5 ± 2.9 mg (0.18 ± 0.10 mg/kg body weight). Consecutive PK studies revealed no significant difference in the mean time to achieve maximum concentrations and the area under the concentration-time curve from 0 to 24 hours (AUC0-24) of both drug formulations. However, the mean trough concentration (Cmin) and the maximum concentration of OD-TAC were 22% and 6% lower and higher, respectively, than those of TD-TAC. Therefore, a better correlation was observed between the AUC0-24 and Cmin of OD-TAC than between those of TD-TAC. CONCLUSIONS: After the change from TD-TAC to OD-TAC, the AUC0-24 values were equivalent despite a 22% reduction in Cmin. Cmin may therefore be an excellent predictor in the therapeutic drug monitoring of OD-TAC because of its superior correlation with AUC0-24.

Baseline glomerular sclerosis influences morphological changes, but not level of serum creatinine.

The aim of this study was to investigate whether glomerular sclerosis (GS) at the time of engraftment affects subsequent morphology and clinical course of renal allografts. Eighty-one renal transplant recipients were recruited for this study. Protocol biopsies of the renal allografts were performed at engraftment, as well as at 1, 3, 5, and 7 years after transplantation. All cases were divided into 2 groups based on the presence of GS at engraftment, namely, non-GS and GS groups. Morphological changes in the renal allografts were graded from 0 to 3+ based on the severity of chronic allograft nephropathy (CAN) of the Banff classification based on 5 factors: percentage of GS, extent of interstitial fibrosis, tubular atrophy, arterial intimal thickening, and arteriolar hyalinosis. Furthermore, the level of serum creatinine (s-Cr) at each year was examined by recipient age and gender, donor age and gender, type of donor (living/cadaver), delayed graft function, acute rejection within 1 year after transplantation, mean blood pressure, and use of calcineurin inhibitors as well as the presence of GS at engraftment. The extent of GS at engraftment significantly correlated with donor age (P = .0038) but with a weak correlation coefficient. Although the severity of CAN developed gradually in both non-GS and GS groups, differences in morphological changes at engraftment between the 2 groups persisted throughout 7 years. Donor age and recipient gender influenced s-Cr significantly. In conclusion, the presence of GS at engraftment aggravates subsequent morphological changes and affects short-term but not long-term allograft prognosis.

The pathologic impact of tacrolimus on protocol biopsy in renal transplant patients with basiliximab-based immunosuppression.

Forty-two ESRD patients underwent renal transplantation using basiliximab (mean age: 30.6 +/- 18.6 years at transplantation; male: 50%; ESRD duration: 51.6 +/- 13.0 months) between February, 2000 and July, 2003. All patients had a protocol biopsy on the day of transplant, on discharge from the hospital (35.5 +/- 13.2 days), and at 1 year after transplant. The immunosuppression included a calcineurin inhibitor, basiliximab, mycophenolate mofetil (MMF), and methylprednisolone. While 16 patients used tacrolimus (FK group: 29.4 +/- 16.6 years old), 26 patients used cyclosporine (CsA group: 31.4 +/- 20.1 years old). Protocol biopsies were graded according to the Banff 97 classification. The incidence of acute rejection episodes within 1 year was greater in the CsA (15%) than the FK group (6%). Serum creatinine at hospital discharge was similar (CsA: 1.01 +/- 0.59 mg/dL, FK: 0.97 +/- 0.49, p = .18); however creatinine at 1 year differed significantly (CyA: 1.22 +/- 0.88 mg/dL, FK: 0.92 +/- 0.39, P = .03). There was a trend toward an increase in the score of interstitial inflammations in the CsA group, while it remained constant in the FK cohort (P = .05 at 1 year between the two groups). Other pathologic scores (t, ci, ct, cv, ah) did not differ between the groups at 1 year. Although there were no differences in the demographics between the two groups, there were several trends toward better renal function in the FK group.

First living related kidney transplantation results in excellent outcomes for small children.

OBJECTIVE: The aim of this study was to evaluated the outcomes of living related kidney transplantation in small children. MATERIALS AND METHODS: Ten pediatric patients with body weights less than 10 kg received parental kidney transplants (five mothers and five fathers). An intra-abdominal approach was used in nine children and a retroperitoneal approach in one child. Bilateral, left, or right nephrectomy was performed in seven, two, and one child, respectively. Immunosuppression consisted of either cyclosporine (n = 7) or tacrolimus (n = 3) with either mizoribine (n = 4) or mycophenolate mofetil (MMF) (n = 5) or azathioprine (n = 1), and methylprednisolone (n = 10). Antilymphocyte globulin was used in the first series of four children; basiliximab in the most recent five children. RESULTS: All renal allografts functioned immediately after transplantation despite the mismatched size of the large renal allografts. Nine of 10 children were alive with a functional allograft at 6 to 196 months posttransplantation. One child died of intra-abdominal bleeding 5 days posttransplantation. One child has suffered chronic allograft nephropathy 11 years posttransplantation (serum creatinine 3.3 mg/dL). The remaining eight children display good renal function (serum creatinine = 0.2 to 1.43 mg/dL). Steroids were withdrawn in eight of nine children; one child continues on alternative-day therapy. One child (LD55) exceeded the mean standard height. The most recent height standard deviation (SD) scores were superior (-1.75 +/- 1.39 [-3.83 to 0.54]; P < .0082) to those at transplantation (-2.91 +/- 0.79 [-2.00 to -4.14]). CONCLUSIONS: The outcomes of living related kidney transplantation in small children were excellent despite the operative risks and the difficulty of cardiovascular and fluid management. Transplantation for small children appears to result in much better quality of life and growth than dialysis.

High-performance liquid chromatographic resolution of reverse isomers of 1,2-diacyl-rac-glycerols as 3,5-dinitrophenylurethanes.

The resolution of reverse isomers remains a major unsolved problem in glycerolipid chromatography. We have investigated the separation of the reverse isomers of 1,2-diacyl-rac-glycerols under a variety of high-performance liquid chromatography (HPLC) conditions. The reverse isomers of diacylglycerols having various pairs of acyl groups including short and highly unsaturated chains, which were prepared by partial Grignard degradation of the corresponding triacylglycerols, were chromatographed as 3,5-dinitrophenylurethanes. Excellent resolution was achieved for the reverse isomers of very different pairs of acyl groups, such as acetate-palmitate and docosahexaenoate-palmitate, by chiral-phase HPLC on columns containing (R)- and (S)-1-(1-naphthyl)ethylamine polymeric phases, reversed-phase HPLC on a highly efficient C18 column (4 microm particle size) and silver ion HPLC on a silver loaded cation-exchange column. The chiral-phase HPLC also permitted complete enantiomer resolution for all the reverse isomers examined. No satisfactory resolution by any of the HPLC methods, however, was obtained for the reverse isomers possessing minor differences in chain lengths and degree of unsaturation, such as laurate-palmitate and oleate-linoleate. The limitations of resolution and characteristics of elution are described.

Liquid chromatography with particle-beam electron-impact mass spectrometry of diacylglycerol nicotinates.

Several synthetic diacylglycerols and natural mixtures derived from soybean, egg yolk, and bovine liver phosphatidylcholines were examined in the form of nicotinate derivatives by liquid chromatography with particle-beam electron-impact mass spectrometry. High-performance liquid chromatography was carried out in the reversed-phase mode with a base-deactivated octyl-/octadecylsilyl stationary phase. The nature (size and degree of unsaturation) of the acyl residues was readily determined from the mass spectra. Uniquely, the positions of the double bonds could be deduced, although this became increasingly difficult as the degree of unsaturation of diacylglycerols containing mixed acyl residues increased. Reverse 1,2-diacylglycerol isomers could be distinguished by their mass spectra.

Rapid separations of diacyl- and dialkylglycerol enantiomers by high performance liquid chromatography on a chiral stationary phase.

Rapid and practical separations of 1,2- and 2,3-diacyl- and dialkyl-sn-glycerol enantiomers as their 3,5-dinitrophenyl-urethane derivatives were carried out by normal-phase high performance liquid chromatography on a chiral stationary phase, N-(R)-1-(alpha-naphthyl)ethylaminocarbonyl-(S)-valine chemically bonded to gamma-aminopropyl silanized silica. Complete separations of the racemates into enantiomers were achieved for both of the diacyl- and dialkylglycerols within 10 min using a stainless steel column (25 cm long) packed with the 5-mu particles, an isocratic elution with a mixture of hexane/ethylene dichloride/ethanol as a mobile phase and a UV detector. The sn-1,2-enantiomers were eluted ahead of the corresponding sn-2,3-enantiomers. Satisfactory separation of the sn-1,3-diacylglycerols from the corresponding enantiomers and the separation of the homologues differing in acyl and alkyl groups were also observed. The formations of hydrogen bonding and charge transfer complex between the urethane derivatives and the stationary phase may contribute to the enantiomer separations.

Stereospecificity of monoacylglycerol and diacylglycerol acyltransferases from rat intestine as determined by chiral phase high-performance liquid chromatography.

Using chiral phase high-performance liquid chromatography of diacylglycerols, we have redetermined the ratios of 1,2-/2,3-diacyl-sn-glycerols resulting from acylation of 2-monoacylglycerols by membrane bound and solubilized triacylglycerol synthetase of rat intestinal mucosa. With 2-oleoyl[-3H]glycerol as the acyl acceptor and oleoyl-CoA as the acyl donor, 97-98% of the diacylglycerol product was 1,2(2,3)-dioleoyl-sn-glycerol, 90% of which was the sn-1,2- and 10% the sn-2,3-enantiomer. The remaining diacylglycerol (less than 3%) was the sn-1,3-isomer. The overall yield of acylation products was 70%, of which 60% were diacylglycerols and 40% triacylglycerols. With 2-oleylglycerol ether as the acyl acceptor and [1-14C]oleoyl-CoA as the acyl donor, 90% of the diradylglycerol was 1-oleoyl-2-oleyl-sn-glycerol and 10% was the 2-oleyl-3-oleoyl-sn-glycerol. The diradylglycerols made up 96% and the triradylglycerols 4% of the radioactive product. With 1-palmitoyl-sn-glycerol as the acyl acceptor and [1-14C]oleoyl-CoA as the acyl donor, the predominant reaction product was 1-palmitoyl-3-oleoyl-sn-glycerol. The 3-palmitoyl-sn-glycerol was not a suitable acyl acceptor. Both 1,2- and 2,3-diacyl-sn-glycerols were substrates for diacylglycerol acyltransferase as neither isomer was favored when 1,2-dioleoyl-rac-[2-3H]glycerol was used as the acyl acceptor. There was a marked decrease in the acylation of the 1(3)-oleoyl-2-oleyl-sn-glycerol to the 1,3-dioleoyl-2-oleyl-sn-glycerol. It is concluded that neither monoacylglycerol nor diacylglycerol acyltransferase exhibit absolute stereospecificity for acylglycerols as fatty acid acceptors.

Fatty acids and fatty alcohols of wax esters in the orange roughy: specific textures of minor polyunsaturated and branched-chain components.

Open-tubular gas chromatography was carried out on fatty acids and alcohols obtained from wax esters of the orange roughy, Hoplostethus atlanticus, caught at sea off New Zealand. The major (above 5%) components were 16:1(n-7), 18:1(n-9) and (n-7), 20:1(n-9) and (n-7), and 22:1(n-11, n-13) as fatty acids, and 16:0, 18:0, 18:1(n-9), 20:1(n-9) and (n-7), and 22:1(n-11, n-13) as fatty alcohols. The total percentages of the minor components were 10% in the acids and 26% in the alcohols. The 22:1/20:1 ratio of the fatty alcohols obtained in this study was less than 1.0, although the ratio for the Atlantic orange roughy has been reported as being greater than 1.0. The contents of polyenes were as low as 2.48% in the acids and 0.95% in the alcohols, but their compositions showed some specific features. The percentages of the C16-C22 dienes in the total polyenes were remarkably high, 57.7% of these acids and 53.1% of these alcohols. The most important dienes were 18:2(n-6) in the acids and 20:2(n-6) in the alcohols.

Determination of stereochemical configuration of the glycerol moieties in glycoglycerolipids by chiral phase high-performance liquid chromatography.

This study reports a simple and sensitive method for determining the absolute configuration of the glycerol moieties in glycoglycerolipids. The method is based on chiral phase high-performance liquid chromatography (HPLC) separations of enantiomeric di- and monoacylglycerols released from glycosyldi- and monoacylglycerols, respectively, by periodate oxidation followed by hydrazinolysis. The released di- and monoacylglycerols were chromatographed as their 3,5-dinitrophenylurethane (3,5-DNPU) and bis(3,5-DNPU) derivatives, respectively. The derivatives were separated on two chiral phases of opposite configuration, (R)- and (S)-1-(1-naphthyl)ethylamine polymers for diacylglycerols and N-(R)- -(1-naphthyl)ethylaminocarbonyl-(S)-valine and N-(S)-1 -(1-naphthyl)ethylamino-carbonyl-(R)-valine for monoacylglycerols. Clear enantiomer separations, which permit the assignment of the glycerol configuration, were achieved for sn-1,2(2,3)-diacyl- and sn-1(3)-monoacylglycerols generated from linseed oil triacylglycerols by partial Grignard degradation on all the chiral stationary phases employed. Using the method, we have determined the glycerol configuration in the glycosyldiacylglycerols (monogalactosyl-, digalactosyl-, and sulfquinovosyldiacylglycerols) and glycosylmonoacylglycerols (monogalactosyl-, digalactosyl-, and sulfoquinovosylmonoacylglycerols) isolated from spinach leaves and the coralline red alga Corallina pilulifera. The results clearly showed that the glycerol moieties in all the glycoglycerolipids examined have S-configuration (sn-1,2-diacyl- and sn-1-monoacylglycerols). The new method demonstrates that chiral phase HPLC provides unambiguous information on the configuration of the glycerol backbone in natural glycosyldi- and monoacylglycerols, and that the two-step liberation of the free acylglycerols does not compromise glycerol chirality.

Gas chromatographic separation of cholesteryl esters of fatty acids of different degrees of unsaturation.

Cholesteryl esters prepared from the fatty acid methyl esters of linseed oil, pig liver lipids, and Japanese anchory oil have been separated on the basis of their chain lengths and number of double bonds by gas liquid chromatography on a cyanosiloxane SILAR 10C column. The equivalent chain lengths of cholesteryl esters having acyl groups with 14-22 carbons and 0-6 double bonds are presented. A significant influence of the column temperature on the equivalent chain lengths of the polyenoic fatty acid cholesteryl esters has been found. Separation of the cholestanyl and epicholestanyl esters of linseed oil fatty acids, respectively, under the same conditions is also described.

Occurrence of plant sterols in aquatic vertebrates.

Plant sterols were found by gas liquid chromatography in the sterols of five species of aquatic vertebrates; mackerel (Scomber japonicus), rainbow trout (Salmo gairdnerii), smelt (Osmerus dentex), sardine (Sardinops melanosticta) and chimera (Chimera phantasma). The sterols of chimera liver, sardine flesh and sardine viscera contained 9.0, 2.4 and 3.1% of C28 and C29 sterols in addition to 86.7, 96.6 and 95.2% of cholesterol. The occurrence of norcholestandienol, campesterol, beta-sitosterol and C28 stanol was shown by combined gas chromatography-mass spectrometry. Sperm whale (Physeter catodon) sterols consisted of more than 99% cholesterol with only traces of 22-dehydrocholesterol.

CD8 T cell of donor splenocyte mixed with bone marrow cells is more effective than CD4 T cell for induction of donor-specific tolerance in sublethally irradiated mice.

BACKGROUND: We previously demonstrated that even a low dose of bone marrow cells (BMCs) established donor-specific tolerance if mixed with splenocytes (SPLCs). In this study, T-cell subsets CD4 (CD4SP) and CD8 (CD8SP) of donor SPLCs were investigated for their contribution to the enhancement of BMC engraftment leading to donor-specific tolerance in sublethally irradiated mice. METHODS: Sublethally irradiated C57BL/6 recipient mice were intravenously injected BMCs mixing with CD4SP or CD8SP harvested from BALB/c donor mice. The degree of chimerism in the peripheral blood lymphocytes (PBLs) and in the SPLCs was analyzed using FACS, mixed lymphocyte reaction, and skin graft transplantation 3 months after injection. RESULTS: Recipients injected with 3 x 10(6) donor BMCs admixed with 10 x 10(6) donor CD8SP established chimerism. However, recipients injected with the same dose of BMCs admixed with 5 x 10(6) CD4SP, 10 x 10(6) CD4SP, and 5 x 10(6) CD8SP did not established chimerism. CD8SP contained 44% of Ly6A/E (Stem Cell Antigen-1 (Sca-1))-positive cells based on FACS analysis, whereas only 6% of CD4SP were positive for Ly6A/E. MLR supernates of donor SPLCs chimeric mice using admixture with CD8SP dominated by Th2 cytokines. In contrast, mixting with MLR supernates from failed chimera showed dominant Th1 cytokines. CONCLUSIONS: CD8SP seems to make a major contribution to enhance BMC engraftment and induce donor-specific tolerance. Ly6A/E (Sca-1)-positive cells need to be further investigated for their contribution to the establishment of chimerism.

A case of living-related partial liver transplantation using the right gastroepiploic artery for hepatic artery reconstruction.

A 13-year-old boy with liver cirrhosis underwent living-related partial liver transplantation with a left lobe from his mother. A standard hepatic artery reconstruction using the recipient right hepatic artery was anticipated. Unfortunately, the recipient hepatic artery was found to be severely arteriosclerotic and was unsuitable for reconstruction. Instead, the right gastroepiploic artery, measuring 2.0 mm in diameter, was mobilized and was anastomosed to the left hepatic artery of the graft in an end-to-end fashion. Arterial blood flow was satisfactory. The patient's postoperative course was uneventful, and he was transferred to a floor bed on the 5th postoperative day.

Dissociation of brain edema induced by cold injury in rat model: MR imaging and perfusion studies with 14C-iodo-antipyrine.

The purpose of this study is to confirm whether T2-weighted imaging and perfusion imaging, i.e. autoradiogram of 14C-iodoantipyrine, on the course of brain edema correspond to each other or not. Cold injured rat brains were used as a model and were sequentially examined by both methods and compared with each other and with histological specimens. Special focus relies on the time changes in the lesions. High SI of T2-weighted images were observed and the percentages in the high SI area to the total brain area in the same slice were 4.7 +/- 0.31, 5.6 +/- 0.46 and 3.4 +/- 0.42 for 6, 24 and 48 hours, respectively. By contrast, low perfusion areas were indicated in the perfusion study and their percentages were 4.6 +/- 0.55, 5.6 +/- 0.86 and 2.4 +/- 0.35 for 6, 24 and 48 hours, respectively. At 48 hours after cold injury, low perfusion areas were smaller than hi

Olfactory neuroblastoma visualized by Technetium-99m-ECD SPECT.

We describe a case of olfactory neuroblastoma diagnosed by 99mTc-ECD SPECT. Although MRI and CT are very important for delineating these tumors, they are, by no means, specific for neuroblastomas. 131I-MIBG scintigraphy, the standard method for imaging tumors of neural crest origin, also failed to detect a histologically proven esthesioneuroblastoma.

Gas chromatographic resolution of polyunsaturated wax esters based on their degree of unsaturation on Silar 10C.

Wax esters of C28-C44 chain-lengths, and containing 0-7 double bonds, were characterized with equivalent chain lengths [ECL] obtained by GC using a cyanosiloxane, Silar 10C. The ECL of the unsaturated wax esters is significantly dependent upon the column temperature, and selection of an appropriate column temperature permitted adequate resolution of critical pairs differing in the degree of unsaturation or the position of the double bonds.

[Antitumor effect of liposome-entrapped carboplatin after intraperitoneal administration in rats].

We examined the distribution in tissue and antitumor effects of freeze-dried liposome-entrapped carboplatin (Lipo-CBDCA) after intraperitoneal administration to rats bearing AH 130 tumors. Liposomes composed of egg lecithin and cholesterol were used as drug carriers. The serum concentration of platinum was decreased for a short time after the intraperitoneal administration of Lipo-CBDCA. After at least 3 hours, the serum concentration of platinum was higher with free CBDCA intraperitoneal or intravenous administration. The antitumor effects of Lipo-CBDCA were determined in rats with peritoneal dissemination due to AH 130 tumors. Intraperitoneal Lipo-CBDCA prolonged the life span of the tumor-bearing rats. No side effects of the chemotherapy were demonstrated in biochemical and histological studies in the liver, kidney, spleen and small intestine. These results indicate that intraperitoneal chemotherapy with Lipo-CBDCA may be more effective than that with free CBDCA managing in peritoneal dissemination, and may be therapeutically useful without toxic side effects.

[Efficacy of preoperative adjuvant chemotherapy using adriamycin targeting the regional lymph nodes for gastric cancer--lymph node-targeting delivery of adriamycin in rabbits].

Chemotherapy targeting the regional lymph nodes for gastric cancer may be more effective preoperatively than postoperatively since anticancer drugs can be transported to the regional lymph nodes via the lymphatic flow through the stomach. Distribution of Adriamycin (ADR) among the various organs was assessed following its intravenous injection in rabbits. The delivery index of the drug to each organ was assessed by the ratio of the area under the concentration-time curve (AUC) of each organ to the AUC of the regional lymph nodes following the intravenous administration. The delivery index was 0.14 for the stomach, 0.11 for the heart, 0.53 for bone marrow, 0.74 for the spleen, and 0.14 for the liver. These data suggest that preoperative adjuvant chemotherapy by intravenous administration of ADR may be effective in targeting ADR at the regional lymph nodes. Tissue ADR concentrations in the regional lymph nodes were assessed following gastric submucosal administration of ADR in rabbits. The targeting index for the regional lymph nodes was 8.20, measured by the ratio of AUC following a gastric submucosal injection to AUC after the intravenous injection of ADR. This suggests that it may be possible to selectively target chemotherapy to regional lymph nodes by employing a gastric submucosal administration of ADR.