Oxidative stress and neurodegeneration in penile ischaemia

OBJECTIVE

To seek markers of oxidative stress and examine neural structural integrity in chronic penile ischaemia using a rabbit model of arteriogenic erectile dysfunction (ED), as the role of ischaemia in penile neuropathy and the oxidative mechanism of neurodegeneration in ED remains unknown.

MATERIALS AND METHODS

A rabbit model of atherosclerosis‐induced ED was developed by partial balloon de‐endothelialization of the iliac arteries. After 10 weeks, intracavernosal blood flow and erectile function in the arteriogenic ED group were compared with age‐matched controls. Erectile tissues were processed for analysis of oxidative stress markers and nerve fibre density using enzyme immunoassay and immunohistochemical staining, respectively. Oxidative stress‐sensitive genes were determined with quantitative real‐time polymerase chain reaction. Tissue ultrastructure was examined by transmission electron microscopy.

RESULTS

Significant erectile tissue ischaemia, erectile dysfunction, increased levels of oxidative products, and marked nitrotyrosine immunoreactivity was evident in the ED group. Oxidative stress‐sensitive genes encoding hypoxia inducible factor‐1α (HIF‐1α), superoxide dismutase (SOD), aldose reductase (AR) and nerve growth factor (NGF) were up‐regulated in the ischaemic erectile tissue. These changes were associated with collapsed axonal and Schwann cell profiles, neurodegeneration, mitochondrial structural damage, increased caveolae, loss of endothelium, and sporadic vacuolization.

CONCLUSIONS

Neuropathy appears to follow the vascular insult in arteriogenic ED. Neural injury in penile ischaemia involves a neurovascular phenomenon mediated by oxidative free radicals. Mitochondrial structural damage and increased HIF‐1α gene expression may be early signals of oxidative stress and neurodegeneration in ED. Up‐regulation of SOD, AR and NGF may be a coordinated defensive reaction to oxidative radicals that seems to fail to prevent neural injury in the ischaemic penis. Our study introduces the concept of oxidative neurodegeneration in the pathophysiology of arteriogenic ED. Therapeutic strategies to protect penile nerves from free radical incursion may enhance the efficacy of surgical and pharmacological interventions in arteriogenic ED.     

Could more effective use of kidneys recovered from older deceased donors result in more kidney transplants for older patients?

In the face of a severe shortage of kidneys from deceased organ donors that limits access to transplantation for many patients, about one of every seven kidneys (more than 1,500 each year) recovered from deceased donors in the United States are not transplanted. Eurotransplant, which coordinates organ distribution for six countries and a population of about 118 million, discards only one of every 20 kidneys procured for transplantation. We compared kidney procurement, transplants, and discards between January 2000 and June 2003 in the United States and in the Eurotransplant region using the Organ Procurement and Transplantation Network/United Network for Organ Sharing and Eurotransplant databases to examine differences that might account for this wide disparity.     

Ultraviolet fluorescence photography: patterns in established pterygia

PURPOSE: To investigate established pterygia using our newly developed ultraviolet fluorescence photography (UVFP) system. DESIGN: Prospective observational case series. METHODS: setting: Prince of Wales Hospital, Sydney, Australia. study population: Fourteen patients (both eyes) attending the Ophthalmology Clinic at Prince of Wales Hospital for assessment of their established pterygia. There were eight men and six women, with an age range of 26 to 62 years. A total of 15 (75%) of 20 had primary pterygia, and five (25%) of 20 had recurrent pterygia. There were no specific exclusion criteria. observation procedures: Ultraviolet and standard (control) photographs were taken of the nasal and temporal interpalpebral regions bilaterally. main outcome measures: The presence of established pterygia detected by standard photography and the corresponding presence and patterns of areas of fluorescence detected by UVFP. RESULTS: In the 14 patients, 20 established pterygia were identified on standard photography. On UVFP, four patterns of fluorescence of established pterygia were identified. Of the 20 pterygia, six (30%) of 20 demonstrated fluorescence at the leading edge of the pterygium, seven (35%) of 20 demonstrated fluorescence at the limbus, three (15%) of 20 demonstrated fluorescence at both the leading edge and the limbus, and four (20%) of 20 demonstrated no visible fluorescence. CONCLUSIONS: In this study, we describe patterns of fluorescence in established pterygia by UVFP. We hypothesize that the areas of fluorescence represent areas of cellular activity within the pterygium. The patterns of fluorescence may be useful to further understand of pterygium growth and pathogenesis.     

Chiari's pelvic osteotomy in the management of Perthes disease

Authors deal, on the basis of an analysis of 3 own cases and of the literary data, with the indication of Chiari's osteotomy in Perthes' disease. It is stated that the operation is to be performed over the age of 8-9 years, in severe lesion of the femoral head, and if the femoral head is so much flattened, widened and extruded from acetabulum that it can not be centralized with varisation. The operation promotes the rebuilding of the femoral head epiphysis, the biomechanical relations are improved and the early arthrosis can be prevented.     

An audit on HIV antibody test uptake amongst GUM clinic attendees in the West Midland region

We audited the practice of offering, and the uptake of, an HIV antibody test amongst genitourinary medicine clinic patients in the West Midlands region. There were wide variations in the offering (from 14 to 100%) and uptake (18 to 64%) of the test in the different clinics within the same region.     

A humid corridor across the Sahara for the migration of early modern humans out of Africa 120,000 years ago

It is widely accepted that modern humans originated in sub-Saharan Africa approximately 150-200 thousand years ago (ka), but their route of dispersal across the currently hyperarid Sahara remains controversial. Given that the first modern humans north of the Sahara are found in the Levant approximately 120-90 ka, northward dispersal likely occurred during a humid episode in the Sahara within Marine Isotope Stage (MIS) 5e (130-117 ka). The obvious dispersal route, the Nile, may be ruled out by notable differences between archaeological finds in the Nile Valley and the Levant at the critical time. Further west, space-born radar images reveal networks of-now buried-fossil river channels that extend across the desert to the Mediterranean coast, which represent alternative dispersal corridors. These corridors would explain scattered findings at desert oases of Middle Stone Age Aterian lithic industries with bifacial and tanged points that can be linked with industries further to the east and as far north as the Mediterranean coast. Here we present geochemical data that demonstrate that water in these fossil systems derived from the south during wet episodes in general, and penetrated all of the way to the Mediterranean during MIS 5e in particular. This proves the existence of an uninterrupted freshwater corridor across a currently hyperarid region of the Sahara at a key time for early modern human migrations to the north and out of Africa.     

Lung inflation with direct injection of agarose: a technique for simultaneous molecular and morphometric measurements

The usual methods for preparing lungs for morphologic study involve the instillation of fixatives that modifyproteins and RNA such that the tissue is unsuitable for molecular studies. To develop a technique suitable for molecular studies, pieces of adult rat lungs were infiltrated with agarose, glutaraldehyde, or paraformaldehyde and the consistency of alveolar inflation was compared to lungs inflated with 10% formalin. Only direct injection with 1% agarose resulted in comparable inflation of lung tissue and preserved RNA and protein. Thus, this technique enables simultaneous molecular and morphometric analysis of the lung on small pieces of lung tissue in heterogeneous lung diseases.     

Autonomic cardiovascular responses are impaired in women with irritable bowel syndrome

GOALS: This study characterizes cardiovascular autonomic function in women with irritable bowel syndrome (IBS), using standardized techniques. BACKGROUND: Autonomic dysfunction is believed to contribute to abnormal gastrointestinal motility and visceral hypersensitivity in IBS. There is mounting evidence of generalized impairment of autonomic activity in patients with IBS. STUDY: Thirty women aged 39 years (95% C.I. 25-53 years) diagnosed with IBS, and 30 age-matched healthy women were studied. The ratio of low frequency to high frequency heart rate variability domains (LF:HF ratio) was used to represent cardiac sympathovagal activity, and orthostatic testing and sustained isometric handgrip exercise were used as sympathetic stimuli. Parasympathetic activity was represented by the expiratory to inspiratory R-R interval (E:I) ratio during deep breathing at 6 minutes. RESULTS: LF:HF responses to handgrip exercise (316%, C.I. 134% to 498% vs. 107%, C.I. 15% to 153%; P < 0.05) and orthostatic testing (648%, C.I. 520% to 904% vs. 330%, C.I. 140% to 520%; P < 0.05) were higher in IBS patients than controls, and the E:I ratio was significantly lower (1.47, C.I. 1.33-1.61 vs. 1.20, C.I. 1.14-1.26; P < 0.01). CONCLUSIONS: Autonomic cardiovascular function is impaired in IBS, manifest as attenuated cardio-vagal tone, and relative sympathetic excess during stimulated conditions.