Clinical Impact of a Protocolized Kidney Donor Follow-up System.

BACKGROUND: Adequate kidney donor management after donation is increasingly emphasized due to concerns of renal function impairment after nephrectomy with increasing life expectancy. In this study, the clinical impact of a protocolized kidney donor follow-up system by nephrologists was evaluated. METHODS: A total of 427 living kidney donors underwent nephrectomy from January 2010 to December 2014 and were followed for at least 2 years at the Samsung Medical Center. Donors were followed-up by nephrologists after the establishment of a donor clinic with systemized protocols in January 2013. The primary outcomes were incidence of post-donation low estimated glomerular filtration rate (eGFR) and renal function adaptability. Secondary outcomes were changes in compliance and incidence of hyperuricemia and microalbuminuria. RESULTS: The patients were divided into 2 groups according to the time of nephrectomy: the pre-donor clinic period (n = 182) and the donor clinic period (n = 172). Preoperative eGFR in patients in the pre-donor clinic period was higher than that in patients in the donor clinic period. After donation, poor renal adaptation was less frequent in the donor clinic period compared to the pre-donor clinic period. Low eGFR tended to be less common during the donor clinic period. Shorter mean outpatient clinic visit intervals with more visits within 6 months after donation and earlier detection of de novo hyperuricemia were found during the donor clinic period. CONCLUSION: A protocolized donor clinic run by nephrologists may improve post-nephrectomy renal outcomes and compliance and facilitate better management of potential risk factors of chronic kidney disease in donors.

Predictive Factors of Renal Adaptation After Nephrectomy in Kidney Donors.

BACKGROUND: Despite compensatory hyperfiltration in remaining nephrons following donor nephrectomy, some donors show impaired renal adaptation and low estimated glomerular filtration rate (eGFR). We investigated the factors predicting early renal adaptation after nephrectomy and identified kidney donors at risk of inadequate renal adaptation. METHODS: A total of 265 living kidney donors from 2010 to 2013 were retrospectively analyzed. Renal function was serially followed for 6 months after the operation. Regression analyses were performed to identify the independent predictors of low eGFR (eGFR <60 mL/min/1.73 m2) and impaired renal adaptation (%Modification of Diet in Renal Disease [MDRD] <66% of baseline eGFR). RESULTS: A total of 148 donors belonged to the low eGFR group, and changes in eGFR (ΔeGFR) at postoperative (PO) 1 day and 1 month were identified as independent predictors of low eGFR. Impaired renal adaptation was related to age, ΔeGFR PO 2-3 days, and ΔeGFR PO 1 month. Early renal adaptation was associated with age, male gender, and residual kidney computerized tomography angiography (CTA) volume. The best sensitivity and specificity were obtained with a cutoff value of ΔeGFR 31 at PO 1 day and 1 month for predicting low eGFR and with a value of ΔeGFR 27 at PO 2-3 days and 1 month for predicting impaired renal adaptation. CONCLUSIONS: Our study showed that the degree of early renal adaptation determines subsequent renal function in kidney donors. Closer monitoring and management may be required in old or male donors with small residual CTA kidney volume as well as donors with persistent ΔeGFR >27 within 1 month of nephrectomy.

Effects of eupatilin on the contractility of corpus cavernosal smooth muscle through nitric oxide-independent pathways.

Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is one of the main compounds present in Artemisia species. Eupatilin has both antioxidative and anti-inflammatory properties and a relaxation effect on vascular contraction regardless of endothelial function. We evaluated the relaxant effects of eupatilin on the corpus cavernosum (CC) of rabbits and the underlying mechanisms of its activity in human corpus cavernosum smooth muscle (CCSM) cells. Isolated rabbit CC strips were mounted in an organ bath system. A conventional whole-cell patch clamp technique was used to measure activation of calcium-sensitive K+ -channel currents in human CCSM cells. The relaxation effect of eupatilin was evaluated by cumulative addition (10-5  m ~ 3 × 10-4  m) to CC strips precontracted with 10-5  m phenylephrine. Western blotting analysis was performed to measure myosin phosphatase targeting subunit 1 (MYPT1) and protein kinase C-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17-kDa (CPI-17) expression and to evaluate the effect of eupatilin on the RhoA/Rho-kinase pathway. Eupatilin effectively relaxed the phenylephrine-induced tone in the rabbit CC strips in a concentration-dependent manner with an estimated EC50 value of 1.2 ± 1.6 × 10-4  m (n = 8, p < 0.05). Iberiotoxin and tetraethylammonium significantly reduced the relaxation effect (n = 8, p < 0.001 and p = 0.003, respectively). Removal of the endothelium or the presence of L-NAME or indomethacin did not affect the relaxation effect of eupatilin. In CCSM cells, the extracellular application of eupatilin 10-4  m significantly increased the outward currents, and the eupatilin-stimulated currents were significantly attenuated by treatment with 10-7  m iberiotoxin (n = 13, p < 0.05). Eupatilin reduced the phosphorylation level of MYPT1 at Thr853 of MLCP and CPI-17 at Thr38. Eupatilin-induced relaxation of the CCSM cells via NO-independent pathways. The relaxation effects of eupatilin on CCSM cells were partially due to activation of BKCa channels and inhibition of RhoA/Rho-kinase.

Interventions do not enhance medication persistence and compliance in patients with overactive bladder: a 24 weeks, randomised, open-label, multi-center trial.

OBJECTIVES: Anticholinergics are currently the mainstay for the management of overactive bladder (OAB). However, low drug adherence has been noted with these medications. The aim of this study was to determine whether a health education intervention (HEI) could improve drug persistence with anticholinergics in OAB patients. METHODS: We enrolled 682 OAB patients who were randomly distributed into either the HEI plus fesoterodine (HEI) group or the fesoterodine alone (control) group. The HEI consists of four education sections: understanding OAB disease, dietary control, bladder training and understanding anticholinergics. The primary end-point was the difference in drug persistence between the HEI and control groups at 24 weeks. Persistence was defined as a gap ≤ 30 days between successive prescription pills. RESULTS: Among the 682 patients, 210 (30.8%) completed 24 weeks of study. Persistence of the HEI group at 6 months was not statistically higher than that of the control group (40.4% vs. 34.9%, p = 0.181). Compliance at 6 months was also similar between the two groups (38.5% vs. 32.5%, p = 0.128). Using OAB symptom score questionnaire, the efficacy of the two groups was not different at each follow-up (p > 0.05). The global response was similar between the two groups. However, the HEI group was more satisfied with treatment than the control group (p = 0.034). The most common reason for discontinuation was satisfaction with the treatment so that they did not need to follow-up, followed by inadequate efficacy in both groups. Adverse events were reported in 12.3% of patients. CONCLUSIONS: The health education intervention was not effective to increase drug persistence in OAB patients on anticholinergics.

MUC1/SEC and MUC1/Y overexpression is associated with inflammation in Sjögren's syndrome.

OBJECTIVES: To evaluate the expression and localization of MUC1/SEC and MUC1/Y isoforms in labial salivary glands (LSG) from Sjögren's syndrome patients (SS patients), as well as their in vitro expression induced by cytokines. SUBJECTS AND METHODS: Labial salivary gland from 27 primary SS patients and 22 non-SS sicca subjects were studied. Relative MUC1/SEC and MUC1/Y mRNA levels were determined by qPCR and protein levels by Western blotting. Induction of mucin mRNAs was assayed in vitro. Immunohistochemistry was used for localization. RESULTS: Relative MUC1/SEC and MUC1/Y mRNA and protein levels were significantly higher in LSG from SS patients. These mRNAs were induced by cytokines. MUC1/SEC and MUC1/Y were detected in acini apical region of control LSGs, and significant cytoplasmic accumulation was observed in acini of SS patients. MUC1/Y localized in acinar nuclei and cytoplasm of inflammatory cells of LSG from SS patients. A strong positive correlation was observed between cellular MUC1/SEC levels and glandular function determined by scintigraphy. CONCLUSIONS: We show for the first time that MUC1/SEC and MUC1/Y are expressed in LSG of both SS patients and non-SS sicca subjects. The observed overexpression and aberrant localization of MUC1/SEC and MUC1/Y and their induction by pro-inflammatory cytokines may favor the perpetuation of the inflammatory environment that disrupts the salivary glandular homeostasis in SS patients.

Comparisons of apomorphine-induced erection and spontaneous erection in rats by telemetric assessment of intracavernosal pressure.

Although there are several methods for assessing erectile function in rats, the standard methods for telemetric monitoring have not been established. Theoretically assessment of spontaneous erection (SE) seems to be a physiologic method but it needs long measuring time and additional efforts. Apomorphine-induced erection (AIE) is one available and simple method; however, the correlation with SE has not been assessed. We compared erection profiles of AIE and SE in normal and two disease rat models using telemetric assessment of intracavernosal pressure (ICP). Seven-week-old male Sprague-Dawley rats were assigned to normal control, diabetes mellitus (DM) and hypercholesterolemia (HC) group. After 19 weeks a telemetric pressure sensor (C40; Data Sciences) was surgically implanted in the corpus cavernosum. One week later, ICP was recorded in freely moving rats after intraperitoneal apomorphine (100 µg/kg) injection (AIE) or during SE. Sexual events were visually identified and recorded. Only the pressure increases that occurred during sexual behavior were analyzed. We compared the erectile profiles such as duration, maximal ICP and the area under the curve (AUC, area under time × ICP curves). Two-way anova revealed no significant effect of the measuring methods on the mean AUC (F1,43 = 2.756, p-value = 0.104), but a significant effect of different disease models on mean AUC (two-way anova: F2,43 = 12.929, p-value < 0.001) was observed. The mean AUC of normal control rats was significantly higher than that of DM and HC rats (Bonferroni post hoc test: p < 0.001 and p = 0.001, respectively). ICP measurements using a telemetric device showed no significant difference in AUC between AIE and SE. AIE is easy and requires less time than SE measurements. Therefore, AIE could be a useful method to evaluate ICP in rats.

Increased expression of TRPC4 channels associated with erectile dysfunction in diabetes.

In recent reports, an association between altered TRPC channel function and the development of various diabetic complications has drawn the attention of many investigators. The aim of this study was to investigate the expression of TRPC4 channels of corpus smooth muscle (CSM) cells in diabetes, and to evaluate the association between erectile dysfunction (ED) and altered TRPC4 channel function. The expression of TRPC4 in the penile tissue of human, normal and diabetic rat was investigated using RT-PCR, western blotting and immunohistochemistry (IHC). In vivo gene transfer of dominant negative (DN) TRPC4 into the CSM of rat was conducted. In vivo pelvic nerve stimulation was performed to measure erectile function. Expression of TRPC1, TRPC3, TRPC4 and TRPC6 in human and rat CSM tissues was confirmed by RT-PCR, western blot and IHC. In the diabetic rat, the expression levels of mRNA and protein of the TRPC4, and TRPC6 were significantly increased compared to control rats (p < 0.05). The change in TRPC4 expression in the diabetic rats was higher than those of the other TRPC subunits (p < 0.05). The IHC showed that only TRPC4 expression had a higher intensity in the diabetes compared to normal rats (p < 0.05). Gene transfection with TRPC4(DN) into the diabetic rats restored erectile function to levels similar to that of normal controls. Gene expression of TRPC4(DN) in CSM tissue was confirmed by RT-PCR 2 weeks after transfection. This study demonstrated that TRPC4 channel expression increased in the penile CSM cells of diabetic rats. The down-regulation of TRPC4 with DN form restored erectile function in the diabetic rats. The alteration of TRPC4 channel is one of pathophysiology of ED and could be a target for drug development for ED.

The role of intracavernosal injection therapy and the reasons of withdrawal from therapy in patients with erectile dysfunction in the era of PDE5 inhibitors.

There has been little data regarding the role of intracavernosal injection (ICI) treatment, its discontinuation rate and the reasons of withdrawal in patients with erectile dysfunction (ED) in the era of phosphodiesterase type 5 (PDE5) inhibitors. The aim of this study was to investigate the rate of withdrawal and its associated reasons in patients undergoing ICI therapy. Patients who were prescribed with ICI treatment two times or more were included since the introduction of sildenafil in Korea in 1999. Telephone surveys were performed to evaluate intercourse rates, withdrawal rates and their associated reasons, adverse events and the patients' satisfaction with their sex lives after the ICI treatments. Two hundred and ninety-four men were contacted by telephone. The mean age was 61.8 ± 7.9 years with a follow-up duration of 25.6 ± 32.1 months. At the last follow-up, 79.9% had discontinued the treatment. Most patients had previously failed PDE5 inhibitor treatment prior to the ICI therapy, and more than half had two or more risk factors of ED. Adequate penile rigidity after ICI therapy was restored in 60.2% of patients. The reasons for discontinuation of ICI were poor response (43.1%), inconvenience of use (18.3%), switch to other treatments (10.7%), loss of libido (6.7%), adverse events (5.5%) and return of spontaneous erection (2.8%). Pain was the most common adverse event in the withdrawal group, whereas prolonged erection was most common in the continuing group. Following ICI treatment, PDE5 inhibitors were the most common therapeutic option (63.1%). The overall satisfaction rate regarding sex life was significantly high in the treatment-continuing group. In conclusion, patients on ICI treatment had severe ED and high withdrawal rates in the era of PDE5 inhibitors. The most common reason for treatment discontinuation was poor response. Before initiating ICI treatments, sufficient counselling is necessary.

The prevalence of premature ejaculation and its clinical characteristics in Korean men according to different definitions.

This study compared the prevalence of premature ejaculation (PE) diagnosed by the PE diagnostic tool (PEDT) score, self-reporting and stopwatch-recorded intravaginal ejaculation latency time (IELT). It examined the characteristics of males diagnosed with PE by each criterion. A questionnaire survey enrolled 2081 subjects from March to October, 2010. Stopwatch-recorded IELT was measured in 1035 of the 2081 subjects. We aimed to determine whether PE has an influence on the frequency and satisfaction of sexual intercourse, the degree of libido/erectile function and the satisfaction. These factors were evaluated according to different definitions of PE to assess whether the definition used yielded differences in the data. The prevalence of PE, based on a PEDT score of ≥11, self-reporting and stopwatch-recorded IELT of ≤1 min was 11.3%, 19.5% and 3%, respectively. The prevalence of PE diagnoses based on PEDT score and self-reporting increased with age, but stopwatch-recorded IELT-based diagnoses did not. Males experiencing PE showed lower levels of libido, erectile function and frequency and satisfaction of sexual intercourse compared with non-PE males. PE males felt that they did not satisfy their partners in terms of the partners' sexual satisfaction and frequency of orgasm, in comparison with non-PE males. PE is a highly prevalent sexual dysfunction in males. Regardless of whether the PE diagnosis was made on the basis of self-reporting, PEDT score or stopwatch-recorded IELT, subjective symptoms were similar among PE males.

Effects of ginsenoside on large-conductance K(Ca) channels in human corporal smooth muscle cells.

Ginseng was known to be an effective natural product that enhances penile erection. However, the precise biological function and mechanisms of action of ginseng with regard to erectile function remain unknown. The principal objective of this study was to identify ginsenoside (principal molecular ingredients of ginseng)-induced activation of large-conductance K(Ca) channel in human corporal smooth muscle cells, and to determine ginseng's mechanism of action on penile erection. Electrophysiological studies using cultured human corporal smooth muscle cells were conducted. We evaluated the effects of total ginsenosides (TGS) and ginsenoside Rg3 on large-conductance K(Ca) channel by determining whole-cell currents and single-channel activities. There was an increase in outward current dependent on TGS concentration (at +60 mV, 1 µg ml(-1); 168.3±59.3%, n=6, P<0.05, 10 µg ml(-1); 173.2±36.8%, n=4, P<0.05, 50 µg ml(-1); 295.3±62.3%, n=19, P<0.001, 100 µg ml(-1); and 462.3±97.1%, n=5, P<0.001) and Rg3 concentration (at +60 mV, 1 µM (0.78 µg ml(-1)); 222.8±64.8%, n=11, P<0.0001, 10 µM; 672.6±137.1%, n=10, P<0.0001, 50 µM; and 1713.3±234.7%, n=15, P<0.001) in the solution that was blocked completely by tetraethylammonium (TEA). Channel opening in cell-attached mode and channel activity in the inside-out membrane patches was also increased significantly by 50 µg of TGS or 10 µM of Rg3. The results of this study suggested that the activation of large-conductance K(Ca) channels by ginsenoside could be one mechanism of ginsenoside-induced relaxation in corporal smooth muscle.

A new Kondo antiferromagnet Ce(Ni(0.25)In(1.75)).

We find that Ce(Ni(0.25)In(1.75)) crystallizes in the hexagonal AlB(2)-type structure with lattice parameters a = 0.4850(5) nm and c = 0.3908(5) nm. Magnetic susceptibility, electrical resistivity and low-temperature specific heat data reveal that the bulk phase transition at 3.7 ± 0.2 K in Ce(Ni(0.25)In(1.75)) is to an antiferromagnetic state. The magnetic contribution to the resistivity ρ(mag) of Ce(Ni(0.25)In(1.75)) increases as ln(T) when temperature is lowered from room temperature and reaches a plateau at 9 K, followed by a rapid decrease around 4 K. These results associated with a reduction of the Ce magnetic moment and of the magnetic entropy at T(N) suggest that Ce(Ni(0.25)In(1.75)) could be a Kondo antiferromagnet. The Kondo temperature is estimated to be of order 6 K.

Responses of giant freshwater prawn (Macrobrachium rosenbergii) to challenge by two strains of Aeromonas spp.

The virulence of two Aeromonas strains (A. veronii and A. caviae) isolated from the hepatopancreas of apparently healthy giant freshwater prawns (Macrobrachium rosenbergii) was compared using a challenge by injections. For the A. veronii strain, challenge with 3.7 x 10(5) cells/g of body weight led to 100% mortality; for the A. caviae strain, 3.8 x 10(6) cells/g produced 100% mortality. The 50% lethal doses (LD50) were 2.0 x 10(3) cells/g for A. veronii and 51.2 x 10(3) cells/g for A. caviae. Use of different culture media (trypticase soy broth vs prawn muscle extract) did not significantly affect the virulence of A. veronii. Injection of a sublethal dose (1 x 10(3) cells/g) of A. veronii led to a significant decrease in the total hemocyte count (THC) between 4 and 24 h after injection. Saline injections also caused a similar though less decrease in THC. In the first 24 h after injection of A. veronii (1 x 10(3) cells/g), the change in the percentages of granulocytes (both granular cells and semigranular cells) in the hemolymph was significantly different. After a significant initial increase, the percentage of hyaline cells fell by a factor of 4, from 9 to 2%. Phenoloxidase activity increased fourfold immediately after injection and returned to preinjection levels at 24 h.

Phenoloxidase activity of hemocytes derived from Penaeus monodon and Macrobrachium rosenbergii.

The phenoloxidase (PO) activity of hemocyte lysate supernatant (HLS) from both tiger shrimp (Penaeus monodon) and giant freshwater prawn (Macro-branchium rosenbergii) was examined by treating HLS with various factors, such as an increase in temperatures from 25 to 70 degrees C, one of four elicitors (beta-1,3-1,6-glucan, zymosan, heat-killed Vibrio cells, and lipopolysaccharide), trypsin, one of three protease inhibitors (soybean trypsin inhibitor, p-nitrophenyl-p'-guanidinobenzoate, and benzamidine), and one of two divalent cations (Mg2+ and Ca2+). The strongest PO activity in both animals was induced at 37 degrees C, while enzyme activity varied according to the concentration of the elicitors or cations added to the HLS samples. The following optimum concentrations were recorded: lipopolysaccharides at 0.5 mg/ml, both beta-glucan and zymosan at 1 mg/ml, and Vibrio cells at 10(6) cells/ml. In addition, for giant freshwater prawn, PO activity increased when HLS was treated with trypsin and decreased when it was separately treated with three protease inhibitors. However, effects of either trypsin or protease inhibitors did not occur in tiger shrimp. Strongest PO activity occurred in HLS treated with 20 mM of either calcium ion or magnesium ion, and the addition of the two cations led to an increase in enzyme activity; a decrease was noted following the treatment with EDTA. Cytochemical analysis revealed that prophenoloxidase system exists in the granulocytes of both tiger shrimp and giant freshwater prawn.

Glucan-induced disease resistance in tiger shrimp (Penaeus monodon).

Non-specific disease resistance induced by yeast cell wall extract, beta-1,3-1,6-glucan, was demonstrated in the tiger shrimp. In this study beta-1,3-1,6-glucan was administered to shrimps by immersion before culturing and orally during the culturing period. Challenge of the treated shrimps with the virulent pathogens, Vibrio vulnificus and viral agents extracted from the white spot syndrome victims, yielded promising results. The tolerance of glucan-treated shrimps was slightly enhanced to stresses including catching, transport and ammonia. The growth and survival rates of treated and untreated shrimps were not significantly different. Therefore, we suggest that beta-1,3-1,6-glucan can be used as an immuno-stimulant of cultured shrimps and may benefit shrimp farmers.

[Small intestine transplantation. Experimental microsurgical model in rats]. / Transplante de intestino delgado. Modelo experimental microquirúrgico en ratas.

Small bowel transplantation may eventually become the definitive solution for those patients who suffer from irreversible intestinal failure and that currently depend on parenteral nutrition for survival. Microsurgical transplantation models in rats are widely used for the application of a great variety of immunological and physiological tests. Herein we report our experience after 30 intestinal harvestings and 12 intestinal transplantations in rats. The following criteria were established to assess the surgical procedures: operative time (harvesting and back table, cold ischemic time and warm ischemic time), vascular and intestinal complications and gut histology before and after transplantation. Average time for the donor surgery (harvesting and back table) was 97.19 min. Average warm ischemic time (includes vascular anastomoses) was 115 min. Histological assessment after 3, 4 and 5 hours of cold ischemia (lactated Ringer's solution with 2.4% mannitol at 4 degrees C) showed only mild ischemic changes. Two thrombotic complications were observed: one at the site of the portalcava anastomosis and one at the aortic suture. Hypovolemic shock was the most common cause of death (9/12) and there was no survival beyond 48 hours. Post-transplantation gut histology showed moderate ischemic injury. We conclude that the harvesting technique, as well as the preservation method used are adequate to obtain grafts in a fast and reliable fashion. However, the number of rats transplanted in this experience do not permit statistical analysis of morbidity and mortality at the present time.

Transplante de intestino delgado. Modelo experimental microquirúrgico en ratas. / [Small intestine transplantation. Experimental microsurgical model in rats]

Small bowel transplantation may eventually become the definitive solution for those patients who suffer from irreversible intestinal failure and that currently depend on parenteral nutrition for survival. Microsurgical transplantation models in rats are widely used for the application of a great variety of immunological and physiological tests. Herein we report our experience after 30 intestinal harvestings and 12 intestinal transplantations in rats. The following criteria were established to assess the surgical procedures: operative time (harvesting and back table, cold ischemic time and warm ischemic time), vascular and intestinal complications and gut histology before and after transplantation. Average time for the donor surgery (harvesting and back table) was 97.19 min. Average warm ischemic time (includes vascular anastomoses) was 115 min. Histological assessment after 3, 4 and 5 hours of cold ischemia (lactated Ringers solution with 2.4

mannitol at 4 degrees C) showed only mild ischemic changes. Two thrombotic complications were observed: one at the site of the portalcava anastomosis and one at the aortic suture. Hypovolemic shock was the most common cause of death (9/12) and there was no survival beyond 48 hours. Post-transplantation gut histology showed moderate ischemic injury. We conclude that the harvesting technique, as well as the preservation method used are adequate to obtain grafts in a fast and reliable fashion. However, the number of rats transplanted in this experience do not permit statistical analysis of morbidity and mortality at the present time.