Renal vascular effects of frusemide in the rat: influence of salt loading and the role of angiotensin II

We showed recently that post-frusemide (furosemide) natriuresis was associated with a major depression of medullary circulation. In the present study, prior to administration of frusemide the tubular transport of NaCl was modified by loading the animals with 5% saline to elucidate a possible interrelation between the tubular and vascular effects of the drug. Moreover, a possible involvement of the renin-angiotensin system was examined by pharmacological blockade using captopril, an inhibitor of angiotensin converting enzyme (1 mg x kg(-1), I.V.), or losartan, a selective inhibitor of angiotensin AT1 receptor (10 mg x kg(-1), I.V.). The effects of frusemide (0.25 mg x kg(-1) I.V., then the same dose given over 1 h) on renal medullary and cortical circulation (using laser-Doppler flowmetry) and renal excretion of sodium (U(Na)V), water and total solutes were measured in anaesthetised rats. With no pre-treatment, frusemide decreased the medullary flow (36.6 +/- 6.0%) significantly more than the cortical flow (10.1 +/- 1.0%; P < 0.001). The difference between the medulla and cortex was not significant in rats which showed high U(Na)V after hypertonic saline loading (2.0 +/- 0.4 vs. 0.4 +/- 0.1 micromol x min(-1) in non-loaded rats): 21.1 +/- 3.9% and 15.8 +/- 1.5%, respectively. At very high U(Na)V (9.5 +/- 1.1 micromol x min(-1)) the post-frusemide decrease in blood flow tended to be smaller in the medulla (7.6 +/- 7.7%) than in the cortex (16.2 +/- 2.6%). The fall in medullary blood flow was attenuated by pre-treatment with captopril (22.0 +/- 3.3%) and abolished by pre-treatment with losartan (2.8 +/- 11.8%). The decrease in cortical blood flow was not changed by hypertonic saline or angiotensin II blockers. The abolition of the post-frusemide depression of medullary blood flow by previous salt loading confirms the proposed link between tubular transport status and vasoconstriction. A similar modification of the response by blockade of the renin-angiotensin system suggests that the system is involved in the mechanism of medullary vasoconstriction.     

Chromosomal markers as prognostic indicators in transitional-cell carcinomas of the bladder

Clinical-cytogenetic correlations were assessed in 79 patients with transitional cell carcinomas of the bladder to whom cytogenetic analysis of the primary tumor had been successful. High-grade (G2+G3) and high-stage (T2-T4) tumors had in general a higher ploidy level and contained more marker chromosomes, including multiple markers, compared to low-grade (G0+G1) and low stage (Ta+T1) tumors. The early recurrence rate (within 7 months) was significantly higher (p<0.05) in patients whose tumors contained marker chromosomes compared to cases without markers. Also, a significantly higher proportion of patients with marker chromosomes died due to their disease during the study period (follow-up time 30 months) compared to those without markers (84% versus 16%, p<0.005). The results confirm and extend previous studies showing that cytogenetic findings may be an important prognostic indicator in bladder cancer patients.     

“Salt mummification” — atypical method of embalming a corpse

International Journal of Legal Medicine - It is extremely rare for table salt to be used to preserve a dead body in criminal cases. In the case presented here, after the death of his 85-year-old...     

Synthesis and structure evaluation of new complex butylarylpiperazin-1-yl derivatives

A series of arylpiperazine derivatives of 1,16-diphenyl-19-azahexacyclo-[14.5.1.0^2,15.0^3,8.0^9,14.0^17,21]docosa-2,3,5,7,8,9,11,13,14-nonaene-18,20,22-trione and 4,10-diphenyl-1H,2H,3H,5H-indeno[1,2-f]isoindole-1,3,5-trione was synthesized. The pharmacological profile of compound 4 at the 5-HT_1A receptor was measured by binding assay. The title compounds were tested in cell-based assay against the human immunodeficiency virus type-1. The X-ray crystallographic studies of derivatives 2, 6, 7, 11, 19, and 20 were presented.     

Mechanical stretch induces myelin protein loss in oligodendrocytes by activating Erk1/2 in a calcium-dependent manner

Myelin loss in the brain is a common occurrence in traumatic brain injury (TBI) that results from impact-induced acceleration forces to the head. Fast and abrupt head motions, either resulting from violent blows and/or jolts, cause rapid stretching of the brain tissue, and the long axons within the white matter tracts are especially vulnerable to such mechanical strain. Recent studies have shown that mechanotransduction plays an important role in regulating oligodendrocyte progenitors cell differentiation into oligodendrocytes. However, little is known about the impact of mechanical strain on mature oligodendrocytes and the stability of their associated myelin sheaths. We used an in vitro cellular stretch device to address these questions, as well as characterize a mechanotransduction mechanism that mediates oligodendrocyte responses. Mechanical stretch caused a transient and reversible myelin protein loss in oligodendrocytes. Cell death was not observed. Myelin protein loss was accompanied by an increase in intracellular Ca²⁺ and Erk1/2 activation. Chelating Ca²⁺ or inhibiting Erk1/2 activation was sufficient to block the stretch-induced loss of myelin protein. Further biochemical analyses revealed that the stretch-induced myelin protein loss was mediated by the release of Ca²⁺ from the endoplasmic reticulum (ER) and subsequent Ca²⁺-dependent activation of Erk1/2. Altogether, our findings characterize an Erk1/2-dependent mechanotransduction mechanism in mature oligodendrocytes that de-stabilizes the myelination program.     

Loss of p14<Superscript>ARF</Superscript> expression in melanoma

Lack of p14ARF expression or its functional inactivation has been observed in human and murine carcinomas. Although very few mutations of p14ARF have been detected in some cancer types, changes in expression seem to play an important role in the development of other human cancers such as mesotheliomas. To examine the p14ARF gene and expression of p14ARF protein in melanomas, we screened eight human melanoma cell lines and primary human melanocytes by RT-PCR, sequencing and immunoblotting. All melanoma cell lines analyzed expressed wild-type p14ARF mRNA as well as protein. P14ARF expression was investigated by immunohistochemical staining of 32 tissue samples of benign melanocytic nevi (n=14), melanomas (n=12) and melanoma metastases (n=6). In contrast to the results obtained from cell lines in vitro the immunohistochemical stainings revealed a correlation between the progression of melanoma and the lack of the p14ARF protein expression. Positive p14ARF protein staining was observed in 11 of 14 benign nevi, in 3 of 12 melanomas and in 0 of 6 melanoma metastases. In summary, we demonstrated a significant inverse correlation between p14ARF protein expression and progression of melanocytic tumors since the amount of p14ARF protein staining decreased from benign melanocytic nevi to metastatic melanoma in situ. These results suggest that p14ARF inactivation is important in the development of melanomas.     

External and iatrogenic trauma of the urinary bladder: a survey in Poland

OBJECTIVE: To assess incidence of urinary bladder injuries (frequently associated with pelvic trauma and often iatrogenic) in Poland. MATERIALS AND METHODS: The records and details of urinary bladder injuries treated between 1995 and 1999 were analysed for 61 urological departments in Poland. RESULTS: During the 5-year period 512 patients had urinary bladder injuries; in 210 (41%) the injury was caused by a road traffic accident, in eight (2%) by compression (crushing injury) within the limits of the pelvic bones, in 40 (8%) by a fall from a height, in three by a gunshot wound and in the remaining 251 (49%) the injury was iatrogenic. Among the 261 bladder injuries that were not iatrogenic, 41 (16%) were associated with pelvic bone trauma. In 36 patients there was simultaneous injury of the urinary bladder and posterior urethra, constituting 14% of such injuries and 7% of all trauma cases. The iatrogenic injuries were in 98 patients (39%) in urological departments, in 130 (52%) women in gynaecological departments and in 23 (9%) on surgical wards. The injury was open in 102 patients (20%) and closed in 372 (73%); there was bladder contusion in 38 patients (7%). The injuries were intraperitoneal in 225 patients (44%) and extraperitoneal in 287 (56%). For diagnosis, abdominal ultrasonography was used in 455 (89%) patients, intravenous pyelography in 266 (52%), cystography in 388 (76%) and computed tomography in 15 (3%). The delay between trauma and diagnosis was 0.5-124 h. Surgical treatment of the injury comprised a monolayer suture of the bladder wall in 51 patients (10%), a two-layered suture in 461 (90%), perivesical drainage in 468 (91%) and inspection of the peritoneal cavity in 232 (45%). The mean (range) interval between diagnosis and treatment was 14 (7-70) days. Seven patients died after the treatment failed. CONCLUSIONS: Almost half the patients had iatrogenic injuries, of which over half occurred in gynaecological and maternity wards. Thus it is important teach the basic range of urological operations to trainee doctors. The commonest diagnostic method was not ascending cystography but ultrasonography; we recommend ascending cystography be used with at least two views after filling the urinary bladder with approximately 300 mL of contrast medium, with an additional film after emptying the contrast medium. In patients with pelvic bone trauma it is reasonable to use spiral computed tomography with virtual analysis before surgery. A two-layered suture of the bladder wall with perivesical drainage should be used.     

Prevalence and treatment of bleeding complications in chronic pancreatitis

Objectives As spontaneous major haemorrhage in patients with chronic pancreatitis is rare, limited data have been reported, and no evidence-based guidelines are currently available regarding the optimal treatment modality.Patients and methods We report our experience with 36 patients with severe bleeding complications from a series of 541 patients presenting with chronic pancreatitis (representing a prevalence of 6.7% of admitted patients), treated in one surgical department over a period of 9.5 years, with a median follow-up of 4.1 years.Results Haemorrhage was indirectly related to chronic pancreatitis in eight patients (22.2%) with ulcer or variceal bleeding. Three patients (8.4%) demonstrated spleen infarction or rupture. The most common causes of major haemorrhage were pseudoaneurysms in 25 patients (69.4%). Nine of them were treated with primary embolization. Sixteen patients with pseudoaneurysms underwent surgery. The only mortalities (8.3%) observed were from bleeding-associated complications of pseudoaneurysms. Two patients died after surgery, and one after primary embolization. We observed a higher re-bleeding rate after surgery (25% vs 11% after embolization). The presence of haemorrhagic shock, and the amount of blood transfused, were significant determinants of hospital mortality. Patient age, pseudoaneurysm location, and treatment modality had no significant influence on mortality.Conclusions Any haemodynamically stable patient with haemorrhage due to arterial pseudoaneurysms should undergo angiography with embolization when technically possible. If there are no other pancreas-related indications for surgery, embolization remains the definitive treatment. If embolization is not available or has failed, surgery is indicated, although perioperative morbidity will be higher.     

Macular corneal dystrophy including histologic and ultrastructural changes

PURPOSE: The study reports the results of a histological and ultrastructural examination of the corneal button, obtained during penetrating keratoplasty from patient with clinically recognized macular corneal dystrophy. MATERIAL AND METHODS: 34-year-old male patient suffering from macular corneal dystrophy (MCD) has been treated on corneal epithelium defect and photophobia since his early childhood. Visual acuity was decreased on the Snellen test chart to 0.02. Slit-lamp examination, and ultrasonographical measurement of the cornea's thickness were performed. Removed during penetrating keratoplasty corneal button was divided into two pieces. One of them was prepared in standard procedure for histological examination in the light microscopy after having been stained with hematoxylin and eosin, alcian blue and paS-method. From the other part, slides for ultrastructural examination in the transmission electron microscopy were prepared with the use of standard method. The family history from the patient was also taken, and available relatives have undergone examination in search of typical MCD symptoms. RESULTS: Slit-lamp examination findings revealed diffuse, from limbus to limbus, stromal opacification. In measurement by pachymeter cornea's thickness was reduced. In the light microscopy, in typical stained slides, delaminations within stroma and deficit of endothelial cells were observed. After being stained with alcian blue, dark blue deposits in the places of delamination became visible. By transmission electron microscopic examination, intracellular and extracellular deposits were detected in the stroma, Descemet membrane and endothelium. Distended keratocytes with enormous vacuoles containing abnormal material were found. Pedigree was typical for autosomal recessive inherited disease. CONCLUSIONS: Histological and ultrastructural diagnosis is a basis of recognition of macular corneal dystrophy. Analysis of the pedigree as well as ultrasonographical measurement of the cornea's thickness is very helpful to establish the right diagnosis.