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Reactive oxygen species (ROS) have been implicated in behaviors induced by acute or repeated cocaine or methamphetamine administration in rodents. In the present study, we investigated the involvement of ROS in behavioral changes induced by nicotine administration and dopamine (DA) transmission changes in the nucleus accumbens (NAc) of rats. Rats were given repeated saline or nicotine (0.4 mg/kg) administration once daily for seven days, and the induction of hyperlocomotor activity, and oxidative stress marker expression induced by the increase in ROS production in the NAc were measured on day 7. We also tested the effect of ROS scavengers on repeated nicotine-induced hyperlocomotor activity and nicotine self-administration, and DA levels in the NAc. Repeated nicotine administration induced hyperlocomotor activity and decreased the expression of oxidative stress markers, such as superoxide dismutase-1 and glutathione peroxidase 1/2, by elevating ROS production in the NAc. Pretreatment with the nonspecific ROS scavenger PBN and the superoxide-selective scavenger TEMPOL significantly attenuated nicotine-induced hyperlocomotor activity without impairing motor function in nicotine-naïve rats on day 7. In addition, in intravenous nicotine self-administration study, TEMPOL significantly reduced nicotine-taking behavior without affecting food intake in nicotine-naïve rats. Furthermore, TEMPOL pretreatment prevented nicotine effects on stimulated DA release in the NAc, which was associated with nicotine-induced behavioral changes. Taken together, these findings suggest that increased ROS production in the NAc contributes to the neuropharmacological properties of nicotine., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All procedures regarding the handling and use of animals in the present study were conducted as approved by the Institutional Animal Care and Use Committee (IACUC) of the Korea Institute of Toxicology (KIT; No. 2112–0049 and 2112–0055)., (© 2025. The Author(s).)

Background and Purpose: α-Pyrrolidinobutiothiophenone (α-PBT) is a chemical derivative of cathinone, a structural analogue of amphetamine. Until now, there have been a few previous neurochemical or neurobehavioural studies on the abuse potential of α-PBT., Experimental Approach: We examined the abuse potential of α-PBT by measuring psychomotor, rewarding, and reinforcing properties and methamphetamine-like discriminative stimulus effects in rodents using locomotor activity, conditioned place preference, self-administration, and drug discrimination studies. To clarify the underlying neuropharmacological mechanisms, we measured dopamine levels and neuronal activation in the dorsal striatum. In addition, we investigated the role of the dopamine D 1 receptor or D 2 receptors in α-PBT-induced hyperlocomotor activity, conditioned place preference, and the methamphetamine-like discriminative stimulus effect of α-PBT in rodents., Key Results: α-PBT promoted hyperlocomotor activity in mice. α-PBT induced drug-paired place preference in mice and supported self-administration in rats. In a drug discrimination experiment, α-PBT fully substituted for the discriminative stimulus effects of methamphetamine in rats. Furthermore, α-PBT increased dopamine levels and c-Fos expression in the dorsal striatum of mice, which was associated with these behaviours. Finally, pretreatment with the D 1 receptor antagonist SCH23390 or the D 2 receptors antagonist eticlopride significantly attenuated acute or repeated α-PBT-induced hyperlocomotor activity, place preference, and the methamphetamine-like discriminative stimulus effects in rodents., Conclusions and Implications: These findings suggest that α-PBT has abuse potential at the highest dose tested via enhanced dopaminergic transmission in the dorsal striatum of rodents. The results provide scientific evidence for the legal restrictions of the recreational use of α-PBT., (© 2024 British Pharmacological Society.)

The chronic use of the novel synthetic cathinone mexedrone, like other psychoactive drugs, can be considered addictive, with a high potential for abuse and the ability to cause psychological dependence in certain users. However, little is known about the neurobehavioral effects of mexedrone in association with its potential for abuse. We investigated the abuse potential for mexedrone abuse through multiple behavioral tests. In addition, serotonin transporter (SERT) levels were measured in the synaptosome of the dorsal striatum, and serotonin (5-HT) levels were measured in the dorsal striatum of acute mexedreone (50 mg/kg)-treated mice. To clarify the neuropharmacological mechanisms underlying the locomotor response of mexedrone, the 5-HT2A receptor antagonist M100907 (0.5 or 1.0 mg/kg) was administered prior to the acute injection of mexedrone in the locomotor activity experiment in mice. Mexedrone (10-50 mg/kg) produced a significant place preference in mice and mexedrone (0.1-0.5 mg/kg/infusion) maintained self-administration behavior in rats in a dose-dependent manner. In the drug discrimination experiment, mexedrone (5.6-32 mg/kg) was fully substituted for the discriminative stimulus effects of cocaine in rats. Mexedrone increased locomotor activity, and these effects were reversed by pretreatment with M100907. Acute mexedrone significantly increased c-Fos expression in the dorsal striatum and decreased SERT levels in the synaptosome of the dorsal striatum of mice, resulting in an elevation of 5-HT levels. Taken together, our results provide the possibility that mexedrone has abuse potential, which might be mediated, at least in part, by the activation of the serotonergic system in the dorsal striatum., Competing Interests: Declaration of competing interest The authors declare no competing interests related to the present study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: With the revision of the Organ and Transplantation Act in 2018, the hand has become legal as an area of transplantable organs in Korea. In January 2021, the first hand allotransplantation since legalization was successfully performed, and we have performed a total of three successful hand transplantation since then. By comparing and incorporating our experiences, this study aimed to provide a comprehensive reconstructive solution for hand amputation in Korea., Materials and Methods: Recipients were selected through a structured preoperative evaluation, and hand transplantations were performed at the distal forearm level. Postoperatively, patients were treated with three-drug immunosuppressive regimen, and functional outcomes were monitored., Results: The hand transplantations were performed without intraoperative complications. All patients had partial skin necrosis and underwent additional surgical procedures in 2 months after transplantation. After additional operations, no further severe complications were observed. Also, patients developed acute rejection within 3 months of surgery, but all resolved within 2 weeks after steroid pulse therapy. Motor and sensory function improved dramatically, and patients were very satisfied with the appearance and function of their transplanted hands., Conclusion: Hand transplantation is a viable reconstructive option, and patients have shown positive functional and psychological outcomes. Although this study has limitations, such as the small number of patients and short follow-up period, we should focus on continued recovery of hand function, and be careful not to develop side effects from immunosuppressive drugs. Through the present study, we will continue to strive for a bright future regarding hand transplantation in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Synthetic cathinones are chemical derivatives of cathinone, a structural analog to amphetamine. It has been shown that synthetic cathinones have abuse potentials similar to psychomotor stimulants such as amphetamine and induce neuroinflammation. Among the novel synthetic cathinones, α-pyrrolidinopentiothiophenone (α-PVT) has been known to produce rewarding and reinforcing effects in rodent models. However, it has not yet been determined whether α-PVT induces neuroinflammation in vivo. In the present study, mice were exposed to repeated saline or α-PVT (20 mg/kg, intraperitoneally) for 7 days to test changes in locomotor activity and neuroinflammation-related factors in the striatum of mice. Repeated administration of α-PVT significantly induced locomotor sensitization. In addition, repeated α-PVT administration significantly increased the number of microglial cells, accompanied by marked increases in TLR1, TLR4, TLR6, and TLR7 mRNA levels in the striatum of mice. Furthermore, acute or repeated α-PVT administration increased the levels of phosphorylated NF-κB, ERK, p38, and JNK MAPK activation and repeated α-PVT, but not acute, increased the levels of TNF-α and IL-6 mRNA in the striatum of mice. Finally, systemic administration of TAK-242 (5 mg/kg, i.p.) or MPLA (50 μg/kg, i.p.), each an inhibitor or activator of TLR4, did not change α-PVT-induced behavioral sensitization in mice. These results suggest that the activation of TLR4 by repeated α-PVT administration may lead to neuroinflammation via TLR-mediated NF-κB and MAPK signaling pathways and the production of TNF-α and IL-6 in the striatum of mice, at least without the regulation of behavioral sensitization., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nicotine, the primary addictive substance in tobacco, produces the psychomotor, rewarding, and reinforcing effects of tobacco dependence by stimulating nicotinic acetylcholine receptors (nAChRs) in the brain. The present study determined that α4β2 nAChRs regulate locomotor sensitization by altering dopamine concentration in the nucleus accumbens (NAc) after systemic challenge exposure to whole cigarette smoke condensate (WCSC). Rats were administered subcutaneous injection of WCSC (0.2 mg/kg nicotine/day) for 7 consecutive days and then re-exposed to WCSC after 3 days of withdrawal. Challenge exposure to WCSC significantly increased locomotor activity. This increase was decreased by the subcutaneous injection of the α4β2 nAChR antagonist, DHβE (3 mg/kg), but not by the intraperitoneal injection of the α7 nAChR antagonist, MLA (5 mg/kg). In parallel with a decrease in locomotor activity, blockade of α4β2 nAChRs with DHβE decreased dopamine concentration in the NAc which was elevated by challenge exposure to WCSC. These findings suggest that challenge WCSC leads to the expression of locomotor sensitization by elevating dopamine concentration via stimulation of α4β2 nAChRs expressed in neurons of the NAc in rats., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: Transplantation coordinators are essential professionals who play a wide range of roles in organ transplantation. Their burnout levels have been shown to be very high due to the significant uncertainty they experience at work. The taxing conditions that accompany their position can increase turnover, which can, in turn, lead to a decrease in the number of experts working in the field. This calls for an improved understanding of their turnover intentions., Methods: We collected data of 80 transplantation coordinators and measured their intolerance of uncertainty, burnout, turnover intention, and grit. The data were analyzed using a multiple regression analysis., Results: A mediation model was confirmed in which intolerance of uncertainty significantly increases burnout, which, in turn, increases turnover intention. The moderating effects of grit on the relationship between intolerance of uncertainty and turnover intentions were also found to be significant. When grit was low, overall turnover intention was high, regardless of intolerance of uncertainty. Conversely, when grit was high, the intention to leave was high only when the intolerance of uncertainty was also high., Conclusions: There is a high level of uncertainty among transplantation coordinators due to the nature of the work; however, the degree to which the uncertainty is accepted varies individually. It is therefore necessary to seek ways to manage the uncertainty at an organizational and personal level. These efforts could contribute to improving transplantation coordinators' long-term service and expertise., Competing Interests: Conflict of Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2020 The Korean Society for Transplantation.)

Overexpression of myeloid cell leukemia-1 (Mcl-1) in cancers correlates with high tumor grade and poor survival. Additionally, Mcl-1 drives intrinsic and acquired resistance to many cancer therapeutics, including B cell lymphoma 2 family inhibitors, proteasome inhibitors, and antitubulins. Therefore, Mcl-1 inhibition could serve as a strategy to target cancers that require Mcl-1 to evade apoptosis. Herein, we describe the use of structure-based design to discover a novel compound (42) that robustly and specifically inhibits Mcl-1 in cell culture and animal xenograft models. Compound 42 binds to Mcl-1 with picomolar affinity and inhibited growth of Mcl-1-dependent tumor cell lines in the nanomolar range. Compound 42 also inhibited the growth of hematological and triple negative breast cancer xenografts at well-tolerated doses. These findings highlight the use of structure-based design to identify small molecule Mcl-1 inhibitors and support the use of 42 as a potential treatment strategy to block Mcl-1 activity and induce apoptosis in Mcl-1-dependent cancers.

WDR5 is a chromatin-regulatory scaffold protein overexpressed in various cancers and a potential epigenetic drug target for the treatment of mixed-lineage leukemia. Here, we describe the discovery of potent and selective WDR5-WIN-site inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified several chemically distinct hit series that bind to the WIN site within WDR5. Members of a 6,7-dihydro-5 H-pyrrolo[1,2- a]imidazole fragment class were expanded using a structure-based design approach to arrive at lead compounds with dissociation constants <10 nM and micromolar cellular activity against an AML-leukemia cell line. These compounds represent starting points for the discovery of clinically useful WDR5 inhibitors for the treatment of cancer.

Myeloid cell leukemia 1 (Mcl-1), an antiapoptotic member of the Bcl-2 family of proteins, has emerged as an attractive target for cancer therapy. Mcl-1 upregulation is often found in many human cancers and is associated with high tumor grade, poor survival, and resistance to chemotherapy. Here, we describe a series of potent and selective tricyclic indole diazepinone Mcl-1 inhibitors that were discovered and further optimized using structure-based design. These compounds exhibit picomolar binding affinity and mechanism-based cellular efficacy, including growth inhibition and caspase induction in Mcl-1-sensitive cells. Thus, they represent useful compounds to study the implication of Mcl-1 inhibition in cancer and serve as potentially useful starting points toward the discovery of anti-Mcl-1 therapeutics.

Two dogs presented to the emergency service after accidental ingestion of afloqualone tablets, a muscle relaxant used for back pain in humans. Toxic effects of the drug in these dogs included vomiting, respiratory depression, seizures, ataxia, bradycardia, and hematuria. Treatment consisted of fluid diuresis, furosemide, and propofol. Flumazenil, a gamma-amino butyric acid antagonist, was administered intravenously; however, it was not effective in stopping the seizures in these dogs. Both dogs recovered with supportive treatment. To the authors' knowledge, this is the first documented report of afloqualone intoxication in dogs.

Objective: Early and proper diagnosis of cancer is the most critical factor for the survival and treatment of veterinary cancer patients. In this study, we evaluated extracellular cyclic AMP-dependent protein kinase A (ECPKA) level in serum as a useful cancer biomarker in dogs., Methods: ECPKA levels were detected in sera from dogs with cancers (n = 48), benign tumours (n = 18), and non-tumour diseases (n = 102) as well as healthy control dogs (n = 54) utilizing enzyme-linked immunosorbent assay (ELISA)., Results: Sera from dogs bearing various types of cancer exhibited markedly increased levels of ECPKA by up to 7.1-, 8.8-, and 10.9-fold compared with those from dogs harbouring benign tumours, dogs with non-tumour diseases, and healthy control dogs, respectively (P < .0001). In addition, serum ECPKA level did not show statistically significant correlation with gender, breed, or age of dogs or their non-cancerous disease conditions., Conclusion: Our data strongly propose that detection of serum ECPKA level is a potential and specific diagnostic tool for cancer in dogs., (© 2017 John Wiley & Sons Ltd.)

Background: A high prevalence of cholestatic disease, including gallbladder mucocele (GBM), has been reported in dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH)., Hypothesis/objectives: Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane., Animals: Sixty-five client-owned dogs with naturally occurring PDH., Methods: This was a retrospective, observational case series. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group., Results: The GBM group had more severe clinical signs and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = .003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < .001)., Conclusions and Clinical Importance: Gallbladder disease associated with cholestatic disease is correlated with PDH in dogs, in both its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Severe acute pancreatitis (SAP) is associated with systemic complications and high mortality rate in dogs. Mesenchymal stem cells (MSCs) have been investigated for their therapeutic potential in several inflammation models. In the present study, the effects of canine adipose tissue-derived (cAT)-MSCs in a rat model of SAP induced by retrograde injection of 3% sodium taurocholate solution into the pancreatic duct were investigated. cAT-MSCs labeled with dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchlorate (1 × 10⁷ cells/kg) were systemically administered to rats and pancreatic tissue was collected three days later for histopathological, quantitative real-time polymerase chain reaction, and immunocytochemical analyses. Greater numbers of infused cAT-MSCs were detected in the pancreas of SAP relative to sham-operated rats. cAT-MSC infusion reduced pancreatic edema, inflammatory cell infiltration, and acinar cell necrosis, and decreased pancreatic expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, -6, -12, -17, and -23 and interferon-γ, while stimulating expression of the anti-inflammatory cytokines IL-4 and IL-10 in SAP rats. Moreover, cAT-MSCs decreased the number of clusters of differentiation 3-positive T cells and increased that of forkhead box P3-positive T cells in the injured pancreas. These results indicate that cAT-MSCs can be effective as a cell-based therapeutic strategy for treatment of SAP in dogs., Competing Interests: There is no conflict of interest.

Background: Canine pemphigus foliaceus is an autoimmune antibody-mediated skin disease characterized by acantholysis. The objective of this case report is to present the successful management of steroid refractory pemphigus foliaceus with cytotoxic T-lymphocyte antigen 4 (CTLA4)-overexpressing adipose tissue mesenchymal stem cells (ATMSCs)., Case Presentation: A 10-year-old, 12.3-kg, castrated male Shih Tzu presented with severe pruritus and anorexia. The diagnosis of pemphigus foliaceus was made based on its history, physical examination, and histopathology results of a skin biopsy. Treatment with prednisolone and combination therapy of other immunosuppressive drugs had failed; therefore, immunosuppressive gene, CTLA4 overexpressing ATMSCs (CTLA4-ATMSCs) and/or naive ATMSCs administration was performed with the consent of the owner. ATMSCs were administered 21 times over a period of 20 months with intervals of 2 to 8 week. Prednisolone was gradually tapered concurrently and no relapse of the clinical signs was observed. After the termination of CTLA4-ATMSCs and/or naive ATMSCs treatment, the skin lesions had improved and could be managed with a low dose of prednisolone for 12 months., Conclusion: CTLA4-ATMSCs or naive ATMSCs transplantation may be beneficial as adjunctive therapy to initiate and maintain the remission of skin lesions caused by pemphigus foliaceus in veterinary medicine.

A radical [3 + 2]-divinylcyclopropane annulation cascade has been extended to encompass five D-ring variants of the meloscine/epimeloscine core structure. Representative ABCD tetracyclic intermediates were further elaborated with novel substituted E-rings through subsequent transformations of advanced intermediates that provided opportunities for late-stage variation of the B-ring (lactam) N-substituents which were also developed.

Purpose: The practice of retrieving vital organs from brain-dead donors is legally and medically accepted in Korea, but health care professionals' beliefs and opinions regarding these matters have not been sufficiently explored. The purpose of this study was to evaluate the knowledge and attitudes of health care professionals to the concepts of brain death and organ retrieval., Methods: Data were collected using a 41-item questionnaire during a week in June 2011. Sixty-one doctors and 109 nurses from five hospitals with more than 2000 beds in Seoul, Korea, participated in the survey. The data was analyzed using SPSS version 17.0 (SPSS Inc. Chicago, Illinois, USA)., Results: There were statistically significant differences in the scores on knowledge according to marital status (P = .001) education level (P = .019), whether the participants were informed about organ donation from a brain-dead donor (P = .002), and the participant's experience managing potential brain-dead patients (P = .037). There were statistically significant differences in the scores on the attitude according to gender (P < .001), age (P < .001), marital status (P < .001), education level (P = .003), job position (P < .001), and the participant's experience referring brain-dead patients to the hospital-based organ procurement organization (P = .001). Significantly, attitude's positively correlated with knowledge about brain-dead organ donation (P < .001)., Conclusion: Compared with previous studies, the knowledge and attitudes of health care professionals' regarding brain death and organ retrieval were not improved. There are passive attitudes to brain death and organ retrieval. More research must be performed to promote knowledge and understanding toward brain death and organ retrieval among health care professionals., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The role of lymphocyte cross-matches (LCM) remains controversial in the liver transplant field. The aim of this study was to correlate the risk for acute rejection episodes and graft survival in liver transplantation with pretransplant LCM results., Patients and Methods: We enrolled 184 adult liver transplantation patients, excluding pediatric and second grafts. The 129 living donor and 55 deceased donor liver transplantations were divided into 2 groups: LCM (+); (n=20) and LCM (-); (n=164)., Results: There were no differences in the demographic features, such as gender and recipient age, original disease, Model for End-Stage Liver Disease score, donor type, number of human leukocyte antigen mismatches, and cold ischemia times. There were no hyperacute rejection episodes in the LCM (+) group. Also, posttransplant complications such as acute rejection episode, biliary complication, or hepatic artery thrombosis were not different. Acute rejection episodes occurred in 5.0% of the LCM (+) group and 15.2% of the LCM (-) group (P=.317). Bile duct complications after transplantation arose in 20.0% of the LCM (+) group and in 32.9% of the LCM (-) group (P=.312). The 2 groups showed no difference in graft survival rate analyzed by the Kaplan-Meier method according to LCM results., Conclusion: Pretransplant LCM results were not associated with overall graft survival or acute rejection episodes in this study., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The construction of two libraries of triazole-containing isothiazolidine 1,1-dioxides is reported utilizing either a one-pot click/aza-Michael or click/OACC esterification protocol. One core dihydroisothiazole 1,1-dioxide scaffold was prepared rapidly on multigram scale via ring-closing metathesis (RCM) and was subjected to a one-pot multicomponent click/aza-Michael protocol with an array of amines and azides for the generation of a 180-member triazole-containing isothiazolidine 1,1-dioxide library. Alternatively, three daughter scaffolds were generated via the aza-Michael of three amino alcohols, followed by a one-pot, multicomponent click/esterification protocol utilizing a ring-opening metathesis polymerization (ROMP)-derived coupling reagent, oligomeric alkyl carbodiimide (OACC) to generate a 41-member library of triazole-containing isothiazole 1,1-dioxides.

The development of a ring-opening metathesis/ring-closing metathesis/cross metathesis (ROM-RCM-CM) cascade strategy to the synthesis of a diverse collection of bi- and tricyclic sultams is reported. In this study, functionalized sultam scaffolds derived from intramolecular Diels-Alder (IMDA) reactions undergo metathesis cascades to yield a collection tricyclic sultams. Additional appendage based diversity was achieved by utilizing a variety of CM partners.

The incidence of malignancy in transplant recipients is known to be higher than the same in the general population. However, the types of malignancies vary geographically, and the relative risks (RR) for malignancy in transplant recipients, compared with that of the general population, also differ country-by-country. In this study, we investigated the incidence and characteristics of malignancies after renal transplantation in a single center. A total of 2630 renal recipients who underwent surgery between April 1979 and June 2007 were enrolled in this study. The cumulative and interval incidences of malignancies were calculated for every 3 years post-transplantation. One-hundred ninety cases of postrenal transplant malignancies among 177 recipients (6.73%) were reported until 2007. The post-transplant malignancies were detected from 6 to 290 months after transplantation, with a mean duration of 112.6 +/- 66.0 months. Skin cancer [35 (18.4%)] was the most common post-transplant malignancy, followed by thyroid [25 (13.2%)], stomach [22 (11.6%)], colorectal [22 (11.6%)], and urologic cancers [19 (10.0%)]. As the post-transplant period increased, the interval incidence of malignancy correspondingly increased. Virus-related malignancies, such as Kaposi's sarcoma and cervical cancer, developed earlier within the post-transplant period, while urologic cancer, colorectal cancer developed late in the post-transplant period. The recipient's age at the time of transplantation was the sole independent risk factor for post-transplant malignancy based on the multivariate analysis (RR = 2.723, P < 0.0001 in the >50-year-old age group). We should establish strategies for post-transplant malignancy-screening based on the recipient's age at the time of transplantation, the post-transplant interval, and the national trend of post-transplant malignancy.

The development of new methods to skeletally diverse sultams based on a central α-halo benzene sulfonamide building block is reported. Several salient features of this building block are utilized in multiple reaction pathways, including the Heck reaction, C- and O-arylation, Sonogashira-Pauson-Khand, Sonogashira-intramolecular hydroamination, lithiative cyclization and domino aza-Michael Heck for the generation of 5-, 6- and 7-membered benzofused bicyclic and tricyclic sultams.

Exchange-donor programs may prevent the current loss of many suitable living donors. Both incompatible donor-recipient pairs--with ABO incompatibility or positive cross-matches--and compatible pairs who wish to locate more suitable donors should be encouraged to participate in exchange-donor programs. Advantages and limitations of exchange-donor programs must be carefully explained to prevent interfamilial conflict. Exchange-donor programs may relieve shortages of donor organs and offer good posttransplant outcomes. Therefore, this program should be widely implemented.

A novel fabrication technique, i.e., electrostatic spray pyrolysis (ESP), has been used in this study to prepare calcium phosphate nano powders. Final annealing was done at 400 degrees C for 30 min in air. The hydroxyapatite-forming ability of the annealed powder has been investigated in Eagle's minimum essential medium solution. X-ray diffracton, field emission scanning electron microscope, energy dispersive X-ray spectroscope, and Fourier transform infrared spectroscope were employed to characterize the annealed powders after immersion. The powder with an amorphous structure induced hydroxyapatite formation on their surfaces after immersion for 15 days.

Background: Serum soluble CD30 (sCD30) levels might be a useful marker of immunologic status in pre transplant (Tx) recipients. We retrospectively correlated preTx sCD30 levels (high versus low) on postTx graft survival, incidence of acute rejection, and graft function using stored preTx serum., Methods: Of 254 recipients who underwent kidney Tx, 120 recipients were enrolled under the uniform criteria (living donor, age >25 years, viral hepatitis free, diabetes free)., Results: The preTx sCD30 was not significantly associated with differences in graft survival rate during 47.5+/-11.4 months of follow-up (P = 0.5901). High sCD30 (> or =115 U/ml) was associated with a higher incidence of clinically or pathologically defined acute rejection than low sCD30, but the difference was not statistically significant (33.9% vs. 22.4%, P = 0.164). The response rate to antirejection therapy in patients with high sCD30 was inferior to those with low sCD30, but also was not statistically significant (33.3% vs. 7.7%, P = 0.087). However, mean serum creatinine levels in high sCD30 patients at one month, one year, and three years postTx were significantly different from those with low sCD30 (P < 0.05). In multiple regression analysis, acute rejection episodes, donor age, kidney weight/recipient body weight ratio, and preTx sCD30 levels were independent variables affecting the serum creatinine level three years postTx., Conclusion: PreTx sCD30 level has a limited effect on the incidence of acute rejection and response to antirejection treatment, but inversely and independently affects serum creatinine level after living donor kidney transplantation.

Using the pretransplant bone mineral density (BMD) data records of renal recipients, we retrospectively examined risk factors affecting posttransplant changes in BMD and the effect of antiosteoporosis management. For 294 kidney transplant recipients from January 1996 to September 2003, BMD values were expressed as spine and femur T-scores. Gender, age, pretransplant diabetes, blood type compatibility, mode and duration of dialysis, and previous transplantation were considered to be variables affecting BMD changes. T-test or ANOVA was used to compare risk factors. At the time of transplantation, mean spine T-scores were significantly lower among the retransplant group. Mean femur T-scores were significantly lower among the retransplant group, older patients (older than 45 years), and female recipients. Prolonged hemodialysis (>12 months) and retransplant were risk factors for BMD loss during the first year posttransplant. Early application of antiosteoporosis management was effective to ameliorate posttransplant BMD loss. However, antiosteoporosis management after 1 year posttransplant was relatively ineffective. Pretransplant evaluation of BMD and the possibility of significant BMD loss during the first posttransplant year should not be overlooked. Prophylaxis against bone loss and treatment should be started as soon as possible after transplantation for recipients with either normal or abnormal pretransplant BMD.

Kidney donation from female donors to male recipients has been reported to be associated with decreased allograft survival. Whether there was a gender-related inadequacy between donor nephron supply and recipient functional demand was investigated in this study. One hundred ninety-five living donor kidney transplant recipients that had neither ischemic injury, episode of rejection, nor any complication were included. Weights and heights of both donors and recipients were recorded to calculate body surface area, lean body weight, and body mass index. The donated kidney was weighed just after cold flush, and the recipient's serum creatinine (Scr) was measured on a daily basis post-operatively. When the recipient's Scr reached the baseline, a 24-h urine was collected for the amount of proteinuria (Upr), creatinine excretion (Ucr) and creatinine clearance (Ccr) calculation. The effect of donor and recipient gender was analysed by independent sample t-test. On average, male donors and recipients were heavier and taller than females. However, the mass of kidneys donated from men and women were not statistically different. The gender-related differences in post-transplant Scr and Ucr of recipients were associated with the differences in the parameters of metabolic demands of recipients rather than with the weight of implanted kidney (renal mass supply) or with pre-operative renal functions of donors (functional supply). The early graft function is not determined by donor gender. The effect of recipient gender on the graft function depends on the metabolic demands, which are higher in male recipients.

Background: Graft mass has been demonstrated to be a determinant of outcome after kidney transplantation. An insufficient nephron might fail to meet the metabolic demands of the recipient and lead to hyperfiltration., Methods: The study population was restricted to live donor transplants demonstrating immediate function that had neither ischemic injury, episodes of rejection, nor any complications that resulted in a functional decrease of the graft. The donated kidney was weighed just after cold flush, and the recipient's serum creatinine (Scr) was measured on a daily basis postoperatively. When the recipient's Scr reached the baseline, the recipient's 24-hour urine was collected for the amount of proteinuria (Upr), creatinine excretion (Ucr), and creatinine clearance (Ccr) calculation. As the parameters of the metabolic demands of donor and recipient, body weight, height, body surface area, lean body weight, and body mass index were noted. Pearson correlation and linear regression were carried out., Results: The graft function, as measured by Scr, Ucr, and Upr, was not directly correlated with the graft weight but rather correlated with the ratios of graft weight to the parameters of recipient's metabolic demands. As recipient size increased, the metabolic demand has increased. The parameters of recipient's metabolic demands were directly correlated with Scr and Ucr, rather than with Upr., Conclusion: During living donor and recipient matching, both the potential sizes of the donated kidney and the recipient should be considered in terms of the early graft function after transplantation.