Adrenomedullin inhibits pressure-induced mesangial MCP-1 expression through activation of protein kinase A

BACKGROUND: In glomerular hypertension, monocyte chemoattractant protein-1 (MCP-1) has been implicated in glomerulosclerosis progression. High-pressure load and stretch on mesangial cells (MC) are two major effects of increased glomerular pressure. We previously reported that pressure per se could induce MCP-1 expression in cultured MC, suggesting the involvement of glomerular hypertension in renal disease progression through MCP-1 expression in MC. We also showed that adrenomedullin (AM) inhibited pressure-induced MC proliferation; however, it is not clear whether AM alters pressure-induced mesangial MCP-1 expression. In this study, we examined the effect of AM on pressure-induced MCP-1 expression in cultured rat MC and the mechanism of such action. Using compressed helium, pressure was applied to MC placed in a sealed chamber. AM inhibited pressure-induced MCP-1 mRNA expression, measured by reverse transcribed-polymerase chain reaction (RT-PCR), in a dose-dependent manner. This inhibition was in parallel to an increase in cellular cyclic AMP (cAMP) levels evoked by AM. The effects of forskolin and dibutyryl cAMP mimicked those of AM. Protein kinase A (PKA) inhibitor H-89 significantly weakened the effects of AM. AM significantly reduced the pressure-induced increase in MCP-1 protein in supernatants of cultured MC, measured by enzyme-linked immunosorbent assay (ELISA). Our results suggested that AM inhibits pressure-induced mesangial MCP-1 expression through PKA activation.     

Reductions in bone turnover, mineral, and structure associated with mechanical properties of lumbar vertebra and femur in glucocorticoid-treated growing minipigs

The present study was designed to determine the effects of glucocorticoid (GC) on bone turnover, minerals, structure, and bone mechanical properties in minipigs. Six 8-month-old G?ttingen minipigs were subcutaneously injected with prednisolone (PN, 0.5 mg/kg body wt (BW)/day, 5 days/week for 26 weeks (Group GC)), 6 were treated with vehicle alone (Group VC), and 4 were sacrificed at start of the study for baseline controls (Group BC). The increase in BW was similar in all groups. PN significantly reduced serum osteocalcin and urinary type-1 collagen N-telopeptide levels at 13 weeks and thereafter, compared with baseline and control, and also reduced serum bone specific alkaline phosphatase levels relative to baseline. At 26 weeks, the longitudinal axis of the lumbar bone and length of femur were smaller in Group GC than Group VC. The total cross-sectional area of femur, but not the lumbar bone, in Group GC was significantly different from Group VC. BMD of the femur, but not L2, measured by DXA, was lower in Group GC than in Groups BC and VC. The cortical shell structure measured by 2D-micro-CT deteriorated and age-dependent increases in trabecular bone structure 3D micro-CT were reduced by PN. PN also caused deterioration of the cortical structure of the mid-femur. In L2 and femur, PN significantly reduced the ultimate load and maximum absorption energy of the femur and L2 compared with Group VC. The structural modulus in Group GC was lower than in Group BC. Regression analyses revealed that bone minerals, bone structure, and chemical markers correlated with mechanical properties of L2 and mid-femur. Our results indicate that PN reduced systemic bone formation and resorption and suppressed the age-dependent increases in bone minerals, structure, and mechanical properties of L2 and mid-femur. Reduced bone turnover seemed to be associated with a reduction in mechanical properties. The growing minipig could be a suitable model of GCs-induced osteoporosis in humans.     

Applied anatomy of the fasciocutaneous branch of the third perforator artery of the deep femoral artery

A study of the anatomy of the fasciocutaneous branch of the third perforator artery of the deep femoral artery was performed to help the elaboration of a fasciocutaneous flap for the reconstruction of skin and subcutaneous and deep fascia of the knee and popliteal region.Forty thighs in 27 fresh cadavers were dissected. In all of the thighs, the third perforator artery was found to arise from the deep femoral artery and reach the posterior aspect of the thigh after perforating the adductor magnus muscle. At that point it was also found that the third perforator artery gives off a branch that emerges through the intermuscular septum between the vast lateral muscle and the long head of the biceps femoral muscle, then crosses the posterior cutaneous nerve and moves directly on to perforate the deep fascia and then to bifurcate into two other branches: one ascending and one descending.The cutaneous area of the flap of the thigh’s posterior region, nourished by the fasciocutaneous branch, was evaluated through the injection of dye. Dying of the upper medial, middle medial, lower medial and lower lateral areas of the flap was not successful in all of the dissected thighs. Nevertheless, the upper lateral and the middle lateral areas were dyed successfully in all 40 dissected thighs of the 27 cadavers.     

Effect of nicotine treatment and withdrawal on random-pattern skin flaps in rats

BACKGROUND: Tobacco use is associated with a high incidence of skin necrosis after surgery. The ideal timing for the cessation of tobacco use before plastic surgery has not, however, been precisely determined. The aim of this work was to define the ideal duration of nicotine withdrawal prior to random-pattern skin flap surgery in rats. METHODS: Groups of 11 animals were subcutaneously injected with saline or nicotine (2mg/kg) twice a day and subjected to random-pattern skin flap surgery according to the following protocol: Group I: continuously injected with saline 4 weeks before and 1 week after the surgery; Group II: injected with nicotine for 4 weeks until the day of the surgery; Group III: injected with nicotine for 4 weeks until one day before the surgery; Group IV: injected with nicotine for 4 weeks until 5 days before the surgery; Group V: injected with nicotine for 4 weeks until 10 days before the surgery; Group VI: continuously injected with nicotine for 4 weeks before and 1 week after the surgery. McFARLANE skin flaps were performed on the dorsal skin, and the rats were sacrificed 1 week after the surgery. RESULTS: The necrotic area was smaller in group I (8.85cm(2)) than in group II (12.15cm(2)), III (12.88cm(2)) and VI (14.84cm(2)) (ANOVA p<0.0001). There was no difference between groups I, IV (10.13cm(2)) and V (9.27cm(2)). CONCLUSIONS: In conclusion, 5 days before surgery was considered the ideal time for nicotine withdrawal in this experimental model.     

Coronary artery-cardiac chamber shunt: cineangiographic analysis

Coronary artery-cardiac chamber shunts (CA-CC shunts) were observed in 101 out of 2267 consecutive patients (4.5%) receiving selective coronary angiography. In these patients, contrast medium injected into the coronary artery escaped directly into the cardiac chamber. CA-CC shunts were angiographically classified into the following two types. Type I: The endocardial layer was diffusely opacified, and contrast medium escaped into the cardiac chamber on systole (n=83). Type II: Contrast medium escaped directly into the cardiac chamber via an undilated branch (n=11). Type I and type II shunts were observed simultaneously in 7 patients. It is speculated that type I is a shunt via a persistent arterio-sinusoidal vessel, while type II is a shunt via a persistent arterio-luminal vessel. Both types were observed frequently (24.9%) in hypertrophic cardiomyopathy. The degree of CA-CC shunts in hypertrophic cardiomyopathy was not influenced by the presence or absence of myocardial squeezing. CA-CC shunts are considered to be due to an abnormality in the coronary microcirculation of the myocardium. We describe the angiographic features of the two types of CA-CC shunt and discuss their pathophysiological significance.     

The Proliferation and Differentiation of Neonatal Epidermal Melanocytes in F1 Hairless Mice of HR-1 × HR/De in Serum-Free Culture

To investigate the characteristics of the proliferation and differentiation of epidermal melanocytes in F₁ hairless mice of HR-1 × HR/De parents in vitro, cell suspensions of the neonatal epidermis were cultured in a serum-free medium supplemented with dibutyryl adenosine 3‘,5‘-cyclic monophosphate (DBcAMP) and/or basic fibroblast growth factor (bFGF). The differentiation of melanocytes was induced by treatment with DBcAMP. In contrast, the sustained proliferation of melanoblasts was induced by combined treatment with DBcAMP and bFGF. The melanoblasts could be subcultured in serum-free medium supplemented with the two factors in the presence of keratinocytes, but not in their absence. This is the first report of successful culture of melanoblasts and melanocytes from hairless mice; it is expected to be useful in understanding the mechanism of the development of pigmented spots in the epidermis of (HR-1 × HR/De) F₁ mice, which are reported to be induced by repeated exposure to ultraviolet light B.     

Trichilemmal Carcinoma on the Thigh: Report of a Case

A 79-year-old Japanese man with a trichilemmal carcinoma (TC) on the right thigh is described. To the best of our knowledge, he is the fifth patient with a TC on the thigh reported from Japan.     

Vitamin C and oxidative stress on cultured human keratinocytes

The aim of this research was to study the hypoxia-induced oxidative stress on cultured human keratinocytes. Control and cultured human keratinocytes were treated with vitamin C, and were then assessed by determining the concentration of malonyl dialdehyde (a final product of lipid peroxidation) existing in the cultured environment. Forty-eight flasks with culture of keratinocytes in confluent layer were divided into four groups: one control and one experimental group treated with vitamin C, and one control and one experimental group without vitamin C. All the cultures were sampled for malonyl dialdehyde assessment immediately after the end of a 30 min period of hypoxia. The statistical analysis of the results showed that vitamin C was not an effective protective agent against oxidative stress caused by hypoxia.     

Leiomyosarcoma of the urinary bladder in a patient with bilateral retinoblastoma

Abstract:   We report a case of bladder leiomyosarcoma in a 27-year-old woman who had previously been treated with surgery and radiation for bilateral retinoblastoma. The patient was admitted to hospital with discomfort on micturition. Cystoscopy revealed a bladder tumor covered by normal urothelium. Transurethral resection of the bladder tumor was performed, and the histopathological diagnosis was leiomyosarcoma. Partial cystectomy was performed. The leiomyosarcoma of the bladder did not invade the muscle layer. However, bladder tumors recurred at new intravesical locations repeatedly. After transurethral resection of the bladder tumor had been performed twice, total cystectomy and creation of an ileal conduit were performed.