Regenerative Effect of Bone Marrow-derived Mesenchymal Stem Cells in Thioacetamide-induced Liver Fibrosis of Rats.

The present study determined the regenerative effect of bone marrow-derived stem cells (BMSCs) on thioacetamide (TA)-induced liver fibrosis in rats. A total of 30 male Wistar rats were randomly divided into sham control and treatment groups. The rats of the sham control group were subdivided into three groups and sampled on the 14th, 18th, and 20th weeks after fibrosis induction. The rats of the treatment group were subdivided into two groups and sampled on the 4th and 6th weeks after BMSCs treatment. Fibrosis was induced by the intraperitoneal administration of 200 mg/kg of TA twice a week for a period of 14 weeks. All the animals underwent liver function tests and histopathologic evaluation 4 and 6 weeks after BMSCs transplantation. The BMSCs were characterized using osteogenic induction and reverse transcription-polymerase chain reaction. The BMSCs were plastic adherent, spindle-shaped, and positive for osteogenic differentiation. They expressed CD73 and were negative for CD45. The infiltration of inflammatory cells and deposition of collagen fibers were noticed after TA administration. A significant decline in inflammatory cells and a healing process were detected 4 weeks after cell transplantation. The amelioration in hepatic tissue was significant 6 weeks after cell therapy. Following the injection of BMSCs, a nonsignificant decrease was visible in aspartate transaminase level; however, this decline was significant for alanine aminotransferase level. The alkaline phosphatase and albumin levels showed an increasing trend after cell administration. The transplantation of BMSCs resulted in a significant regenerative effect after hepatic injuries. Therefore, it was shown that BMSCs transplantation can open a new window and be a therapy of choice in the amelioration of liver fibrosis.

Comparison of Renal Growth, Proteinuria and Graft Survival between Recipients of Pediatric and Adult Cadaveric Kidney Transplants.

BACKGROUND: The shortage of cadaveric kidney donors has prompted transplant teams to expanding the donor selection criteria. The usage of pediatric cadaveric kidneys is one of those expanded criteria. But the main concern is the probability of hyperfiltration syndrome due to small renal mass of pediatric donors. OBJECTIVE: To compare the graft and patient survivals, post-transplantation complications, rate and severity of proteinuria secondary to hyperfiltration injury and the kidney growth of recipients who underwent transplantation from adult (group 1) and pediatric deceased donors (group 2). METHODS: In this historical cohort study, each group contains 36 patients. Outcome measures included patient and graft survivals, quality of graft function as assessed by serum creatinine (SCr) and estimated GFR (eGFR), surgical complications, proteinuria that was detected by routine urinalysis and then confirmed by a 24-h urine protein >150 mg, blood pressure, and kidney length and volume measured by early and follow-up ultrasonography. RESULTS: The mean donor age in groups 1 and 2 was 36 and 6.5 years, respectively. 9 (25%) kidneys taken from pediatric donors (group 2) were offered en-bloc. The mean follow-up was 28 month. The two groups were not significantly different in terms of the incidence of DGF, rate of acute rejection, 1-year graft survival, SCr and eGFR levels, rates of surgical complications requiring surgical interventions, development of proteinuria, and rate of post-transplantation rise in blood pressure. The mean±SD kidney length within 24 hours of transplantation was significantly higher in group 1 compared to group 2 recipients (112±14 vs. 75±12 mm; p=0.001), but the rate of increase in kidney length in group 2 was significantly higher than that in group 1 recipients (43±4 vs. 10±2 mm; p=0.002) during the follow-up period. 80% of the increase in the kidney size was observed during the first 12 months of surgery; another 20% happened between 12 and 18 months. CONCLUSION: We found that obligatory and compensatory growth of pediatric kidney donors can overcome the concern of hyperfiltration syndrome and that the outcome is the same as adult donors.

The Healing Effect of Adipose-Derived Mesenchymal Stem Cells in Full-thickness Femoral Articular Cartilage Defects of Rabbit.

BACKGROUND: Articular cartilage defect can lead to degradation of subchondral bone and osteoarthritis (OA). OBJECTIVE: To determine the healing effect of transplantation of adipose-derived mesenchymal stem cells (Ad-MSCs) in full-thickness femoral articular cartilage defects in rabbit. METHODS: 12 rabbits were equally divided into cell-treated and control groups. In cell-treated group, 2×10(6) cells of third passage suspended in 1 mL of DMEM was injected into articular defect. The control group just received 1 mL of DMEM. Dulbecco's modified Eagles medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin and streptomycin and 2 mM L-glutamine were used for cell culture. To induce cartilage defect, 4 mm articular cartilage full-thickness defect was created in the knee. For histological evaluation in each group (H&E, safranin-O and toluidine blue), 3 rabbits were sacrificed 4 weeks and 3 animals, 8 weeks after cell transplantation. RESULTS: In cell therapy group post-transplantation, no abnormal gross findings were noticed. Neo-formed tissues in cell-treated groups were translucent with a smooth and intact surface and less irregularity. In cell-treated group after 8 weeks post-transplantation, the overall healing score of experimental knees were superior when compared to other groups. CONCLUSION: We showed that Ad-MSCs, as an available and non-invasive produced source of cells, could be safely administered in knee osteochondral defects.

SNP detection in Na/K ATP-ase gene α1 subunit of bisexual and parthenogenetic Artemia strains by RFLP screening.

In order to find a marker for differentiating between a bisexual and a parthenogenetic Artemia strain, Exon-7 of the Na/K ATPase α(1) subunit gene was screened by RFLP technique. The results revealed a constant synonymous SNP (single nucleotide polymorphism) in digestion by the Tru1I enzyme that was consistent with these two types of Artemia. This SNP was identified as an accurate molecular marker for discrimination between bisexual and parthenogenetic Artemia. According to the Nei's genetic distance (1973), the lowest genetic distance was found between individuals from Artemia urmiana Günther 1890 and parthenogenetic populations, making the described marker the first marker to easily distinguish between these two cooccurring species.

Liquid three-phase microextraction based on hollow fiber for highly selective and sensitive determination of using an ion selective electrode.

In this paper, for the first time, a combination of hollow fiber based liquid 3-phase microextraction with a potentiometric method was applied as a highly selective and sensitive method of analysis. Desipramine, as a model compound, was extracted from a small volume in the presence of 0.10 mol L-1 NaOH (donor solution) through a thin phase of propyl benzoate inside the pores of a polypropylene hollow fiber and finally into a 10 µL acidic acceptor solution inside the hollow fiber. Two microelectrodes were designed and inserted into the two ends of a hollow fiber inside the acceptor solution. Potentiometric analysis was performed in situ within an extraction time of 15 min; the final stable signal was used for analytical application. Under the optimized conditions, an enrichment factor of 296 was achieved and the relative standard deviation (RSD%) of the method was 4.5%. The calibration curve was obtained in the range of 3.0 × 10-5 to 3.4 × 10-8 mol L-1 with a reasonable linearity (R2 > 0.9849) and a limit of detection (LOD) of 3.1 × 10-8 mol L-1. Finally, the applicability of the proposed method was evaluated by extraction and determination of desipramine in plasma and urine samples without any special pretreatment.

A comparison of effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on rats' epididiymal and testicular tissues.

The goal of this study was to determine the effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on the structure of testis and epididymis of male rat. After determining tolerance dose of drugs in pilot study, 24 male rats were divided to four groups: ABVD (doxorubicin, bleomycine, vinblastin, dacarbazine) group, ChlVPP (chlorambucil, vinblastin, procarbazine, prednisolone) group and two control groups one for each treatment group. One half of the lethal dose for 50% of population (LD50) was used for treatment of animals in each protocol. Testes and epididymis tissues were examined for structural changes and serum testosterone level was measured by Lission (chemiluminescence method). Body weight, testis and epididymis weights, in treated rats were significantly less than their control groups specifically in ABVD group was less than ChlVPP group. Decreasing of mean diameter of seminiferous tubules, height of spermatogenic cells and diameter of epididymis in caput, corpus and cauda in ABVD group were significantly more than ChlVPP and control group. The serum testosterone level in ABVD group was significantly less than ChlVPP and control group. According to this study results, the ChlVPP had fewer impairment effects than ABVD on testis and epididymis tissue in tolerance doses on male rats' reproductive system. More clinical trial studies are suggested on Hodgkin's patients. With equal treatment effectiveness, it will be better to use the most reliable and safe treatment especially in young patients.

Breast cancer risk factors in south of Islamic Republic of Iran: a case-control study.

A case-control study was carried out from April 2000 to March 2002 to investigate risk factors for breast cancer in Bandar Abbas, south Islamic Republic of Iran. Using logistic regression analysis, 168 women with pathologically confirmed primary breast cancer were compared with 504 age-matched controls. Significant risk factors were: family history of breast cancer in a first-degree relative, younger age at menarche, never married, first full-term pregnancy age 30+ years and >5 full-term pregnancies. In multivariate analysis, negative history of breastfeeding was also significant. Cases and controls did not differ with regard to parity, history of abortion, oral contraceptive use, menopausal status, age at menopause, ever-use of hormone replacement therapy, history of benign breast disease or history of cigarette smoking.

Psychologic well-being of surgery residents after inception of the 80-hour workweek: a multi-institutional study.

BACKGROUND: The 80-hour workweek was adopted by US residency programs on July 1, 2003. Our published data from the preceding year indicated significant impairment in psychologic well-being among surgery residents. The purpose of this study was to determine whether psychologic well-being and academic performance of surgery residents improved after inception of the 80-hour workweek. METHODS: A single-blinded survey of general surgery residents (n=130) across 4 US training programs was conducted after July 1, 2003, with the use of validated psychometric surveys (Symptom Checklist-90-R and Perceived Stress Scale) and the American Board of Surgery In-Training Examination; comparison was done with preceding year and societal data. Primary outcomes were "psychologic distress" and "perceived stress." Secondary outcomes were "somatization," "depression," "anxiety," "interpersonal sensitivity," "hostility," "obsessive-compulsive behavior," "phobic anxiety," "paranoid ideation," "psychoticism." and "academic performance." The impact of demographic variables was assessed. RESULTS: Mean psychologic distress improved from the preceding year (P < .01) but remained elevated, compared with societal norms (P < .001). The proportion of residents meeting the criteria for clinical psychologic distress (>or=90th percentile) decreased from 38% before, to 24% after, July 2003. Mean perceived stress remained elevated, compared with norms (P < .0001) without improvement from the preceding year. Overall academic performance was unchanged. Previously elevated secondary psychologic outcomes improved after July 2003 (P < .05), although obsessive-compulsive behavior, depression, interpersonal sensitivity, hostility, and anxiety failed to normalize. Male gender and single status were independent risk factors for psychologic distress. CONCLUSIONS: Inception of the 80-hour workweek is associated with reduced psychologic distress among surgery residents. The perception of stress and academic performance remains unchanged.

Psychological well-being of surgery residents before the 80-hour work week: a multiinstitutional study.

BACKGROUND: Accreditation Council on Graduate Medical Education work-hour restrictions are aimed at improving patient safety and resident well-being. Although surgical trainees will be dramatically affected by these changes, no comprehensive assessment of their well-being has been recently attempted. STUDY DESIGN: A multicenter study of psychological well-being of surgical residents (n = 108) across four US training programs before implementation of the 80-hour work week was performed using two validated surveys (Symptom Checklist-90-R [SCL-90-R] and Perceived Stress Scale [PSS]) during academic year 2002-03. Societal normative populations served as controls. Primary outcomes measures were psychologic distress (SCL-90-R) and perceived stress (PSS). Secondary outcomes measures (SCL-90-R) were somatization, depression, anxiety, interpersonal sensitivity, hostility, obsessive-compulsive behavior, phobic anxiety, paranoid ideation, and psychoticism. The impact of personal variables (age, gender, marital status) and programmatic variables (level of training, laboratory experience, institution) was assessed. RESULTS: Mean psychologic distress was significantly higher in general surgery residents than in the normative population (p < 0.0001), with 38% scoring above the 90th percentile and 72% above the 50th percentile. Mean perceived stress among surgery residents was higher than historic controls (p < 0.0001), with 21% scoring above the 90th percentile and 68% above the 50th percentile. Among secondary outcomes, eight of nine symptom dimensions were significantly higher in surgical residents than in societal controls. In subgroup analyses, male gender was associated with phobic anxiety (p < 0.001) and anxiety (p < 0.05), and junior level of training (PGY 1 to 3) with anxiety (p < 0.05), obsessive-compulsive behavior (p < 0.05), and interpersonal sensitivity (p < 0.05). CONCLUSIONS: More than one-third of general surgery residents meet criteria for clinical psychologic distress. Surgery residents perceive significantly more stress than societal controls. Both personal and programmatic variables likely affect resident well-being and should be considered in assessing the full impact of Accreditation Council on Graduate Medical Education directives and in guiding future restructuring efforts.

Modification of bone marrow radiosensensitivity by medicinal plant extracts.

Withaferin A (WA), a steroidal lactone, and Plumbagin (Pl), a naphthoquinone, from the roots of Withania somnifera and Plumbago rosea, respectively, have been shown to possess growth inhibitory and radiosensitizing effects on experimental mouse tumours. An aqueous extract of the leaves of Ocimum sanctum (OE) was found to protect mice against radiation lethality. Therefore, the radiomodifying effects of the above plant products on the bone marrow of the adult Swiss mouse was studied. Single doses of WA (30 mg kg-1) or Pl (5 mg kg-1) were injected intraperitoneally (ip) and OE (10 mg kg-1) was injected ip once daily for five consecutive days. Administration of extracts was followed by 2 Gy whole body gamma irradiation. Bone marrow stem cell survival was studied by an exogenous spleen colony unit (CFU-S) assay. The effects of WA and Pl were compared with that of cyclophosphamide (CP) and radioprotection by OE was compared with that of WR-2721 (WR). Radiation reduced the CFU-S to less than 50% of normal. WA, CP and Pl significantly enhanced this effect and reduced the CFU-S to almost the same extent (to < 20% of normal), although individually WA and Pl were less cytotoxic than CP. These results indicate that radiosensitization by WA and Pl is not tumour specific. OE significantly increased CFU-S compared with radiotherapy (RT) alone. OE+RT gave a higher stem cell survival (p < 0.05) than that produced by WR+RT. While WR alone had a toxic effect, OE treatment showed no such effect, suggesting that the latter may have an advantage over WR in clinical application.