Asymptomatic emphysematous pyelitis-a rare clinical entity.

A 62-year-old asymptomatic woman with diabetes was referred to the urology department from nephrology due to deterioration in renal function with accompanied right-sided hydronephrosis on ultrasound. CT imaging subsequently revealed a right-sided staghorn calculus and a significant volume of gas in the right collecting system from the kidney to the distal ureter, in keeping with emphysematous pyelitis. She was admitted and managed with antibiotics and insertion of right nephrostomy in the first instance, followed by percutaneous nephrolithotomy to definitively manage the stone. The patient remained asymptomatic throughout the process.

Evaluating KIND1 human embryonic stem cell-derived pancreatic progenitors to ameliorate streptozotocin-induced diabetes in mice.

BACKGROUND & OBJECTIVES: Diabetes is a global disease burden. Various stem cell types are being explored to serve as an alternative source of islets. This study was conducted to evaluate the ability of in-house developed human embryonic stem (hES) cells-derived pancreatic progenitors to ameliorate diabetic symptoms in mice. METHODS: Pancreatic progenitors were packed in macro-capsules and transplanted into six male Swiss mice and four mice were taken as controls. Thirty days post-transplantation, diabetes was induced by streptozotocin treatment. Mice were then followed up for >100 days and body weight and blood glucose levels were regularly monitored. RESULTS: Control mice lost weight, maintained high glucose levels and did not survive beyond 40 days, whereas transplanted group maintained body weight and four of the six mice had lowered blood glucose levels. About five-fold increase was observed in human C-peptide levels in the recipients of progenitor transplants as compared to diabetic control. INTERPRETATION & CONCLUSIONS: The beneficial effect of transplanted cells was not long-lasting. Further studies are required to critically evaluate and compare the potential of endogenous pluripotent stem cells and hES cells-derived progenitors before moving from bench to the bedside.

Mouse Bone Marrow VSELs Exhibit Differentiation into Three Embryonic Germ Lineages and Germ & Hematopoietic Cells in Culture.

Very small embryonic-like stem cells (VSELs) have been reported in various adult tissues, express pluripotent and primordial germ cells (PGCs) specific markers, are mobilized under stress/disease conditions, give rise to tissue committed progenitors and thus help regenerate and maintain homeostasis. The aim of the present study was to evaluate in vitro differentiation potential of VSELs using a quantitative approach. VSELs were collected from mouse bone marrow after 4 days of 5-fluorouracil (5-FU, 150 mg/Kg) treatment, further enriched by size based filtration and cultured on a feeder support in the presence of specific differentiation media. Cultured VSELs were found to differentiate into all three embryonic germ cell lineages, germ and hematopoietic cells after 14 days in culture. This was confirmed by studying Nestin, PDX-1, NKX2.5, DAZL, CD45 and other markers expression by various approaches. Very small, CD45 negative cells collected and enriched from GFP positive 5-FU treated mice bone marrow transitioned into CD45 positive cells in vitro thus demonstrating that VSELs can give rise to hematopoietic stem cells (HSCs). We envision that VSELs may be responsible for plasticity and ability of bone marrow cells to give rise to non-hematopoietic tissue progenitors of all 3 germ layers. Moreover the ability of VSELs to differentiate into germ cells as well as all the three lineages provides further evidence to support their pluripotent state and confirms developmental link between bone marrow VSELs and PGCs. The property of quiescence, no risk of teratoma formation and autologus source, make pluripotent VSELs a potential candidate to facilitate endogenous regeneration compared to cell replacement strategy envisioned using embryonic and induced pluripotent stem cells.

Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead.

BACKGROUND: Both pluripotent very small embryonic-like stem cells (VSELs) and induced pluripotent stem (iPS) cells were reported in 2006. In 2012, a Nobel Prize was awarded for iPS technology whereas even today the very existence of VSELs is not well accepted. The underlying reason is that VSELs exist in low numbers, remain dormant under homeostatic conditions, are very small in size and do not pellet down at 250-280g. The VSELs maintain life-long tissue homeostasis, serve as a backup pool for adult stem cells and are mobilized under stress conditions. An imbalance in VSELs function (uncontrolled proliferation) may result in cancer. SEARCH METHODS: The electronic database 'Medline/Pubmed' was systematically searched with the subject heading term 'very small embryonic-like stem cells'. OBJECTIVE AND RATIONALE: The most primitive stem cells that undergo asymmetric cell divisions to self-renew and give rise to progenitors still remain elusive in the hematopoietic system and testes, while the presence of stem cells in ovary is still being debated. We propose to review the available literature on VSELs, the methods of their isolation and characterization, their ontogeny, how they compare with embryonic stem (ES) cells, primordial germ cells (PGCs) and iPS cells, and their role in maintaining tissue homeostasis. The review includes a look ahead on how VSELs will result in paradigm shifts in basic reproductive biology. OUTCOMES: Adult tissue-specific stem cells including hematopoietic, spermatogonial, ovarian and mesenchymal stem cells have good proliferation potential and are indeed committed progenitors (with cytoplasmic OCT-4), which arise by asymmetric cell divisions of pluripotent VSELs (with nuclear OCT-4). VSELs are the most primitive stem cells and postulated to be an overlapping population with the PGCs. Rather than migrating only to the gonads, PGCs migrate and survive in various adult body organs throughout life as VSELs. VSELs express both pluripotent and PGC-specific markers and are epigenetically and developmentally more mature compared with ES cells obtained from the inner cell mass of a blastocyst-stage embryo. As a result, VSELs readily differentiate into three embryonic germ layers and spontaneously give rise to both sperm and oocytes in vitro. Like PGCs, VSELs do not divide readily in culture, nor produce teratoma or integrate in the developing embryo. But this property of being relatively quiescent allows endogenous VSELs to survive various kinds of toxic insults. VSELs that survive oncotherapy can be targeted to induce endogenous regeneration of non-functional gonads. Transplanting healthy niche (mesenchymal) cells have resulted in improved gonadal function and live births. WIDER IMPLICATIONS: Being quiescent, VSELs possibly do not accumulate genomic (nuclear or mitochondrial) mutations and thus may be ideal endogenous, pluripotent stem cell candidates for regenerative and reproductive medicine. The presence of VSELs in adult gonads and the fact that they survive oncotherapy may obviate the need to bank gonadal tissue for fertility preservation prior to oncotherapy. VSELs and their ability to undergo spermatogenesis/neo-oogenesis in the presence of a healthy niche will help identify newer strategies toward fertility restoration in cancer survivors, delaying menopause and also enabling aged mothers to have better quality eggs.

Delineating the effects of 5-fluorouracil and follicle-stimulating hormone on mouse bone marrow stem/progenitor cells.

BACKGROUND: Pluripotent, Lin(-)/CD45(-)/Sca-1(+) very small embryonic-like stem cells (VSELs) in mouse bone marrow (BM) are resistant to total body radiation because of their quiescent nature, whereas Lin(-)/CD45(+)/Sca-1(+) hematopoietic stem cells (HSCs) get eliminated. In the present study, we provide further evidence for the existence of VSELs in mouse BM and have also examined the effects of a chemotherapeutic agent (5-fluorouracil (5-FU)) and gonadotropin hormone (follicle-stimulating hormone (FSH)) on BM stem/progenitor cells. METHODS: VSELs and HSCs were characterized in intact BM. Swiss mice were injected with 5-FU (150 mg/kg) and sacrificed on 2, 4, and 10 days (D2, D4, and D10) post treatment to examine changes in BM histology and effects on VSELs and HSCs by a multiparametric approach. The effect of FSH (5 IU) administered 48 h after 5-FU treatment was also studied. Bromodeoxyuridine (BrdU) incorporation, cell cycle analysis, and colony-forming unit (CFU) assay were carried out to understand the functional potential of stem/progenitor cells towards regeneration of chemoablated marrow. RESULTS: Nuclear OCT-4, SCA-1, and SSEA-1 coexpressing LIN(-)/CD45(-) VSELs and slightly larger LIN(-)/CD45(+) HSCs expressing cytoplasmic OCT-4 were identified and comprised 0.022 ± 0.002 % and 0.081 ± 0.004 % respectively of the total cells in BM. 5-FU treatment resulted in depletion of cells with a 7-fold reduction by D4 and normal hematopoiesis was re-established by D10. Nuclear OCT-4 and PCNA-positive VSELs were detected in chemoablated bone sections near the endosteal region. VSELs remained unaffected by 5-FU on D2 and increased on D4, whereas HSCs showed a marked reduction in numbers on D2 and later increased along with the corresponding increase in BrdU uptake and upregulation of specific transcripts (Oct-4A, Oct-4, Sca-1, Nanog, Stella, Fragilis, Pcna). Cells that survived 5-FU formed colonies in vitro. Both VSELs and HSCs expressed FSH receptors and FSH treatment enhanced hematopoietic recovery by 72 h. CONCLUSION: Both VSELs and HSCs were activated in response to the stress created by 5-FU and FSH enhanced hematopoietic recovery by at least 72 h in 5-FU-treated mice. VSELs are the most primitive pluripotent stem cells in BM that self-renew and give rise to HSCs under stress, and HSCs further divide rapidly and differentiate to maintain homeostasis. The study provides a novel insight into basic hematopoiesis and has clinical relevance.

The use of a thermoexpandable metal alloy stent in the minimally invasive management of retroperitoneal fibrosis: a single center experience from the United kingdom.

PURPOSE: To review our experience with and the effectiveness of the ureteral Memokath 051 metallic stent for the minimally invasive management of retroperitoneal fibrosis (RPF). PATIENTS AND METHODS: We retrospectively reviewed the records of patients with RPF who were treated between April 2008 and February 2013. Success was defined as improvement of renal function and lack of complications after stent placement. Follow-up was at 6 weeks, 3 months, 6 months, and annually thereafter. RESULTS: A total of 14 patients were identified. The study included eight female and six male patients. Mean age was 60.2 years±8.4 standard deviation (SD). The majority of patients had idiopathic RPF (n=12, 85.7%). Stent placement was performed in 23 renal units in 14 patients, 9 (64.3%) of whom had bilateral disease. Ten (71.4%) patients had previously received medical treatment, while three (21.4%) presented with recurrent disease postureterolysis. The mean length of follow-up was 22.5 months (range 3-56 mos). Mean stricture length was 7.6 cm±6.2 SD on the right and 7.7 cm±5.1 SD (P=0.925) on the left. Patients tolerated the stents well with minimal discomfort. Ureteral obstruction was managed successfully in 78.6% of patients (n=11/14). All patients had improvement of renal function. CONCLUSIONS: To our knowledge, this is the first study using metal stents in patients with RPF. Retrograde placement of the ureteral Memokath 051 metal stent can be considered as a promising alternative for initial or salvage postureterolysis minimally invasive management of ureteral obstruction in RPF.

Effective management of lower urinary tract dysfunction in idiopathic Parkinson's disease.

Parkinson's disease, also known as paralysis agitans, is a progressive degenerative disorder of the central nervous system, with onset usually between the ages of 50 and 65 years, and is associated with loss of dopaminergic neurons in the subsantia nigra and the presence of Lewy bodies. It is characterized by the triad of resting tremor, muscular rigidity and bradykinesia. Often-accompanying abnormalities include disorders of equilibrium, posture and autonomic function, including micturition. Symptoms from the lower urinary tract add a significant comorbidity factor in these patients. The incidence and prevalence of lower urinary tract dysfunction rise with increasing progression of the underlying neurological disease. They present a troublesome and difficult to treat health issue with a profound impact on the patient's quality of life. Storage symptoms seem to predominate. In the long term, renal function might be compromised, mainly as a result of elevated intravesical pressure. Various conservative, minimally-invasive and surgical treatment options are available to prevent harmful sequelae, and to improve the quality of life of these patients. We present an overview of current and prospective treatment strategies.

Haematospermia - a systematic review.

Haematospermia (or haemospermia) is a distressing symptom in sexually active men. In most cases, it is caused by non-specific inflammation of the prostate and seminal vesicles. In a small percentage of men, however, it may be a manifestation of genito-urinary or systemic malignancy, in particular prostate cancer. The purpose of this review is to explain the causes and management of patients with haematospermia.