Penile Fracture at the Crus of the Penis - A Rare Case Report.

Penile fracture is an uncommon acute surgical emergency, typically occurring after sexual intercourse, self-manipulation and at times, may be accidental. We report here a 39-year male who attended the department of emergency with swelling and bruising of the scrotum and penis. Physical examination exhibited a diffuse abdominal and perineal ecchymosis. Imaging confirmed a crural penile fracture. Operative fixation was performed appropriately and satisfactory erectile function was reported at the follow-up. We report a very rarely documented case involving the penile crus fracture and its management. Key Words: Crus, Penile fracture, Surgical repair.

The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells.

BACKGROUND: Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1+/MAGE-A4-), which fail to differentiate to pre-spermatogonia (POU5F1-/MAGE-A4+) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to investigate the role of Gankyrin in progression from gonocyte to pre-invasive GCNIS and subsequent invasive TGCC. METHODS: We determined Gankyrin expression in human fetal testicular tissue (gestational weeks 9-20; n = 38), human adult testicular tissue with active spermatogenesis (n = 9), human testicular tissue with germ cell maturation delay (n = 4), testicular tissue from patients with pre-invasive GCNIS (n = 6), and invasive TGCC including seminoma (n = 6) and teratoma (n = 7). Functional analysis was performed in-vitro by siRNA knock-down of Gankyrin in the NTera2 cells (derived from embryonal carcinoma). RESULTS: Germ cell expression of Gankyrin was restricted to a sub-population of prespermatogonia in human fetal testes. Nuclear Gankyrin was also expressed in GCNIS cells of childhood and adult pre-invasive TGCC patients, and in GCNIS from seminoma and non-seminoma patients. Cytoplasmic expression was observed in seminoma tumour cells and NTera2 cells. Gankyrin knock-down in NTera2 cells resulted in an increase in apoptosis mediated via the TP53 pathway, whilst POU5F1 expression was unaffected. Furthermore, Gankyrin knock-down in NTera2 cells increased cisplatin sensitivity with an increase in cell death (13%, p < 0.05) following Gankyrin knock-down, when compared to cisplatin treatment alone, likely via BAX and FAS. Our results demonstrate that Gankyrin expression changes in germ cells during normal transition from gonocyte to prespermatogonia. In addition, changes in Gankyrin localisation are associated with progression of pre-invasive GCNIS to invasive TGCC. Furthermore, we found that Gankyrin is involved in the regulation of NTera2 cell survival and that a reduction in Gankyrin expression can modulate cisplatin sensitivity. CONCLUSIONS: These results suggest that manipulation of Gankyrin expression may reduce the cisplatin dose required for the treatment of TGCC, with benefits in reducing dose-dependent side effects of chemotherapy. Further studies are required in order to assess the effects of modulating Gankyrin on GCNIS/TGCC using in vivo models.

Non-invasive treatment in the management of Peyronie's disease.

Peyronies disease (PD) is estimated to affect approximately 3-9% of men worldwide and maybe associated with pain, erectile dysfunction and penile deformity including shortening. The condition has significant debilitating effects on quality of life, self-esteem and psychological wellbeing in addition to sexual function. Surgical results add further to this by patients having dissatisfaction with various aspects of outcomes. Non-surgical management may allow patients to avoid the morbidities associated with surgery and still achieve improved functional and aesthetic outcomes. Several non-surgical options are currently being employed in the treatment of PD that may reduce or stabilize both objective measures (e.g. penile length and deformity) and subjective measures (including sexual function, pain and partner satisfaction). Nonsurgical management can allow patients to avoid the morbidities associated with surgery and still achieve improved functional and aesthetic outcomes. In this article we explore the current non-surgical management options for PD including oral, mechanical therapies, intralesional and topical treatments. We also briefly discuss future treatment options in the form of stem cell therapy.

Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats.

Physical activity and non-exercise activity thermogenesis (NEAT) are crucial factors accounting for individual differences in body weight, interacting with genetic predisposition. In the brain, a number of neuroendocrine intermediates regulate food intake and energy expenditure (EE); this includes the brain melanocortin (MC) system, consisting of MC peptides as well as their receptors (MCR). MC3R and MC4R have emerged as critical modulators of EE and food intake. To determine how variance in MC signaling may underlie individual differences in physical activity levels, we examined behavioral response to MC receptor agonists and antagonists in rats that show high and low levels of physical activity and NEAT, that is, high- and low-capacity runners (HCR, LCR), developed by artificial selection for differential intrinsic aerobic running capacity. Focusing on the hypothalamus, we identified brain region-specific elevations in expression of MCR 3, 4, and also MC5R, in the highly active, lean HCR relative to the less active and obesity-prone LCR. Further, the differences in activity and associated EE as a result of MCR activation or suppression using specific agonists and antagonists were similarly region-specific and directly corresponded to the differential MCR expression patterns. The agonists and antagonists investigated here did not significantly impact food intake at the doses used, suggesting that the differential pattern of receptor expression may by more meaningful to physical activity than to other aspects of energy balance regulation. Thus, MCR-mediated physical activity may be a key neural mechanism in distinguishing the lean phenotype and a target for enhancing physical activity and NEAT.

PCI in a case of dual (type IV) LAD with anomalous origin of the LCx from RCA.

Dual left anterior descending coronary artery (LAD) originating from the left main stem and the right coronary artery (type IV LAD) is a rare congenital anomaly. Its association with an anomalous origin of the left circumflex (LCx) from RCA is even rarer. We describe a patient presenting with acute inferior wall myocardial infarction, who was subsequently found to have this coronary anomaly. He underwent staged PCI of the dominant RCA and anomalous LCx successfully through the radial route. We conclude that anomalous coronaries can be safely and successfully treated through the radial route after careful evaluation of origin and course of the anomalous vessels. CT coronary angiography is extremely useful in delineating the vessel course and particularly their relation to great arteries.

Detection of anti-tuberculosis activity in some folklore plants by radiometric BACTEC assay.

AIMS: The anti-tubercular drugs are less effective because of the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) strains of M. tuberculosis, so plants being an alternative source of anti-microbial compounds. The aim of this study was to investigate anti-tuberculosis potential of the plants using Mycobacterium smegmatis as a rapid screening model for detection of anti-mycobacterial activity and further to evaluate the active plants for anti-tuberculosis activity against M. tuberculosis using radiometric BACTEC assay. METHODS AND RESULTS: The 15 plants were screened for anti-mycobacterial activity against M. smegmatis by the disk diffusion assay. The ethanolic extracts of Mallotus philippensis, Vitex negundo, Colebrookea oppositifolia, Rumex hastatus, Mimosa pudica, Kalanchoe integra and Flacourtia ramontchii were active against M. smegmatis in primary screening. The anti-tuberculosis potential was identified in the leaves extracts of Mallotus philippensis by radiometric BACTEC assay. The ethanolic extract of M. philippensis showed anti-tuberculosis activity against virulent and avirulent strains of M. tuberculosis H(37) Rv and M. tuberculosis H(37) Ra with minimum inhibitory concentration 0·25 and 0·125 mg ml(-1), respectively. The inhibition in growth index values of M. tuberculosis was observed in the presence of ethyl acetate fraction at a minimum concentration of 0·05 mg ml(-1). CONCLUSION: We found that BACTEC radiometric assay is a valuable method for detection of anti-tuberculosis activity of the plant extracts. The results indicate that ethanolic extract and ethyl acetate fraction of M. philippensis exhibited significant anti-mycobacterial activity against M. tuberculosis. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings provide scientific evidence to support the traditional medicinal uses of M. philippensis and indicate a promising potential of this plant for the development of anti-tuberculosis agent.

Palliation of male genital cancers.

Advanced genital tumours are rare. Traditionally, surgical intervention in these patients has had a limited role due to the associated co-morbidities, poor performance status and overall poor prognosis. Because the potential benefit of surgical intervention in advanced cases is not evidence based, a large proportion of these patients are treated palliatively with chemoradiation therapy, which may have a limited role in advanced disease together with no significant improvement in quality of life for the patient. We present a review of palliative surgical techniques and non-surgical interventions in a range of male genital malignancies. Although the focus relates to advanced tumours with a palliative intent, a brief discussion on treatment with a view to cure is also covered. The traditional dogma is challenged with demonstration of value in surgery as part of multimodal therapy. Various surgical techniques that are used not only to excise the primary tumour, but also those of reconstruction of the urinary tract as well as techniques of flap and graft-based coverage are described. We show the essential role of surgery as part of multimodal therapy in well-motivated patients. No longer is surgery considered as having a limited role in these patients with advanced male genital malignancy.

Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues.

Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT-PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases of human prostate cancer and 23 benign prostate specimens. We found increased expression of MMP10, 15, 24, 25 and 26, urokinase plasminogen activator-receptor (uPAR) and plasminogen activator inhibitor-1 (PAI1), and the newly characterised serine proteases hepsin and matriptase-1 (MTSP1) in malignant tissue compared to benign prostate tissue. In contrast, there was significantly decreased expression of MMP2 and MMP23, maspin, and the protease inhibitors tissue inhibitor of metalloproteinase 3 (TIMP3), TIMP4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the cancer specimens. The expression of MMP15 and MMP26 correlated positively with Gleason score, whereas TIMP3, TIMP4 and RECK expression correlated negatively with Gleason score. The cellular localisation of the expression of the deregulated genes was evaluated using primary malignant epithelial and stromal cell cultures derived from radical prostatectomy specimens. MMP10 and 25, hepsin, MTSP1 and maspin showed predominantly epithelial expression, whereas TIMP 3 and 4, RECK, MMP2 and 23, uPAR and PAI1 were produced primarily by stromal cells. These data provide the first comprehensive and quantitative analysis of the expression and localisation of MMPs and their inhibitors in human prostate cancer, leading to the identification of several genes involved in proteolysis as potential prognostic indicators, in particular hepsin, MTSP1, MMP26, PAI1, uPAR, MMP15, TIMP3, TIMP4, maspin and RECK.

Effect of ochratoxin A on Escherichia coli-challenged broiler chicks.

A study was conducted to evaluate the effects of ochratoxin A (OA) on Escherichia coli-challenged broiler chickens. Day-old broiler chicks were separated into two groups of 92 chicks each, with one group fed a control mash diet, and the other fed a mash diet containing 2 ppm OA. On day 14, each group was further separated into two groups, with one group inoculated with E. coli O78 (1 x 10(7) colony-forming units/0.5 ml), whereas the other group was not inoculated with E. coli. After E. coli inoculation on day 14, four birds from each group were euthanatized at 1, 2, 3, 5, 7, 10, 14, and 21 days postinoculation. Escherichia coli infection caused dullness, depression, huddling, and diarrhea. Mortality was 14.3% in chicks infected with E. coli but fed no OA. Mortality increased to 35.7% in chicks fed OA and infected with E. coli. Decreased body weight and reduced feed intake were observed in chicks fed OA, and the effects were more pronounced in chicks fed OA and infected with E. coli. Increased serum levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine and decreased levels of total proteins, albumin, globulins, calcium, and phosphorus were observed in OA-fed birds. Escherichia coli infection did not cause significant alteration in any of the serum biochemical parameters. The presence of OA in poultry rations increased mortality and the severity of an E. coli infection.

Tau, beta-amyloid and beta-amyloid precursor protein distribution in the entorhinal-hippocampal alvear and perforant pathways in the Alzheimer's brain.

It has been suggested that the pathological lesions of Alzheimer's disease (AD) spread along neuronal connections. This study was designed to examine this hypothesis in the alvear and perforant pathways, two well-defined neuroanatomical pathways that project from the entorhinal cortex to the hippocampus. Paraffin-sections of hippocampal-entorhinal cortex from 25 AD cases were immunolabelled for tau, beta-amyloid (Abeta) and beta-amyloid precursor protein (betaAPP). We used image-analysis to quantify immunolabelling at both ends of the alvear and perforant pathways. At the beginning and the end of the alvear pathway, area of immunolabelling in microm2 per area of field (72000 microm2) were as follows: tau 349 and 821 (P<0.01), Abeta 349 and 61 (P<0.05) and betaAPP 18 and 73 (P<0.01). Corresponding values for the perforant pathway were tau 421 and 387, Abeta 382 and 115 (P<0.05) and betaAPP 55 and 83. Tau was significantly greater at the end than at the beginning of the alvear pathway, but similar at both ends of the perforant pathway. There was significantly more Abeta at the beginning than at the end of the alvear and perforant pathway. These results at least in part reinforce previous work [19] that tau-rich areas may be neuronally connected to Abeta-rich areas.

Regional distribution of tau, beta-amyloid and beta-amyloid precursor protein in the Alzheimer's brain: a quantitative immunolabelling study.

Regional variation in the distribution of SP and NFT within the brain is well documented. Consideration of such variation is potentially of help in formulating models of disease progression. Several models propose that pathological changes in Alzheimer's disease (AD) progress in a step-wise fashion along neuronally connected regions. In this study, we measured tau, Abeta and betaAPP load in different brain regions and examined our results against models of AD progression. Blocks of brain tissue from 45 AD and 15 control cases were immunolabelled for tau, Abeta and betaAPP. Immunolabelled areas were measured as a proportion of the area of the field. Tau load was almost twice as great in the entorhinal cortex than elsewhere in the brain and was least in the cingulate gyrus. In contrast, Abeta was greatest in the cingulate gyrus and least in the entorhinal cortex. BetaAPP rankings were similar to those of tau. Thus the site with the greatest Abeta load (cingulate cortex) had the least tau and the site with the greatest tau load (entorhinal cortex) had the least Abeta. The entorhinal and cingulate cortex are neuronally interconnected. Our results might be explained on the basis that a neurone with its cell body in the entorhinal cortex and axonal terminals in the cingulate cortex shows predominately tau pathology in relation to the cell body and predominately Abeta pathology in relation to its axonal terminals. We conclude that our observations are consistent with previously described models of AD progression. It is possible that tau-rich neurones are associated through their projections to Abeta rich sites. Further work of this kind analysing differential pathological profiles in interconnected brain regions may contribute to refining this model.