Experimental platform for investigations of high-intensity laser plasma interactions in the magnetic field of a pulsed power generator.

An experimental platform for the studying of high-intensity laser plasma interactions in strong magnetic fields has been developed based on the 1 MA Zebra pulsed power generator coupled with the 50-TW Leopard laser. The Zebra generator produces 100-300 T longitudinal and transverse magnetic fields with different types of loads. The Leopard laser creates plasma at an intensity of 1019 W/cm2 in the magnetic field of coil loads. Focusing and targeting systems are integrated in the vacuum chamber of the pulsed power generator and protected from the plasma debris and strong mechanical shock. The first experiments with plasma at laser intensity >2 × 1018 W/cm2 demonstrated collimation of the laser produced plasma in the axial magnetic field strength >100 T.

Effect of vitamin D3 on the conversion of ethylene glycol to glycolate and oxalate in ethylene glycol-fed rats.

Hypercalciuria and hyperoxaluria are important risk factors in the pathogenesis of kidney stones. Urinary glycolate has also been reported to be elevated in patients with renal stones. 1,25-Dihydroxyvitamin D(3), the active metabolite of vitamin D, has been reported to induce hyperoxaluria after either oral or intravenous administration. 1-alpha-D(3), a synthetic derivative of vitamin D, together with ethylene glycol, has been reported to induce renal stones in experimental rats. We have examined the effect of 1-alpha-vitamin D(3) on urinary oxalate and glycolate excretion. Our results indicate that 1-alpha-D(3), together with ethylene glycol, caused a significant increase in urinary glycolate, without a parallel rise in urinary oxalate excretion, in ethylene glycol-fed rats. This increase in urinary glycolate was due to the synergistic effect of both drugs.

Growth inhibitory activity of lemnabourside on human prostate cancer cells.

Induction of apoptosis and androgen ablation are two major approaches for treating human prostate carcinoma. In a study of the bioactive components of the soft coral Nephthea chabroli, we found that lemnabourside is a 5alpha-reductase inhibitor, as shown by its ability to inhibit the conversion of testosterone into the more potent dihydrotestosterone in rat prostate homogenate. The compound also inhibited the incorporation of tritiated thymidine into human prostate androgen-dependent carcinoma LNCaP cells, and thus blocking the cell proliferation (IC50 = 37.5 microM). The expression of prostate marker genes, including 5alpha-reductase, prostate-specific antigen, prostatic acid phosphatase and androgen receptor, and the anti-apoptotic bcl-2 gene were markedly reduced, but the transcription of apoptosis-related caspase 3 gene showed a dose-dependent increase in lemnabourside-treated LNCaP cells. Immunofluorescent microscopy and flow cytometric analysis further demonstrated apoptotic changes in these cells. Taken all results together, a relatively weak 5alpha-reductase inhibitory activity on LNCaP cells (EC50 > 250 microM), and a similar growth inhibitory activity on both androgen dependent- and independent-prostate cells (IC50 approximately 37.5 microM) indicated that caspase-3 apoptosis pathway is one of the possible antiproliferative activities mediated by lemnabourside.

Angiotensin regulates endothelin-B receptor in rat inner medullary collecting duct.

Our recent studies showed that endothelin (ET)(B) receptors are downregulated in congestive heart failure. These changes in ET(B) receptor density can be prevented by angiotensin-converting enzyme inhibitors, suggesting a possible role for angiotensin. Using isolated inner medullary collecting ducts (IMCD), we examined the possibility that angiotensin-induced downregulation of ET(B) receptors is accompanied by a decrease in ET(B) receptor mRNA. Binding studies showed that overnight incubation with angiotensin II induced a downregulatiion of ET(A) and ET(B) receptors' density in IMCD by 39% and 29%, respectively. This downregulation in ET receptor density was abolished when IMCD was coincubated with angiotensin II and its receptor antagonist saralasin. Furthermore, when the cells were exposed to phorbol myristate acetate (PMA), it resulted in a reduction in ET(A) and ET(B) receptor binding sites by 41% and 34%, respectively, suggesting the involvement of protein kinase C (PKC). In isolated IMCD, ET-1 induced an increase in cyclic guanosine monophosphate (cGMP) accumulation (705 + 63 to 1,015 + 88 fmol/microg protein/5min, P <.01), and the ET-1-induced accumulation was attenuated in the presence of angiotensin II (641 + 45 to 809 + 46 fmol/microg protein/5min, P <.01). Using competitive polymerase chain reaction (PCR) method, we also observed downregulation of ET(A) and ET(B) receptors mRNA in IMCD treated with angiotensin II (ET(A), 1.09+0.11 v 0.77 + 0.07 amol/microg of total RNA, P <.01; ET(B), 14.80 + 1.95 v 8.65 + 0.67 amol/microg of total RNA, P <.01). The addition of a PKC inhibitor abolished the downregulation of ET(A) and ET(B) receptor mRNA induced by angiotensin II (ET(A), 1.25 + 0.07 v 1.19 + 0.06 amol/microg of total RNA, not significant [NS]; ET(B), 14.36 + 0.83 to 13.68 + 0.64 amol/microg of total RNA, NS). These results suggest that angiotensin II-induced downregulation of ET(A) and ET(B) receptors mRNA is mediated by a mechanism involving PKC.

Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis.

The perivascular epithelioid cell has been proposed to be the unifying proliferating cell type in a number of lesions such as angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumor and renal capsuloma. With the exception of rare examples of angiomyolipoma, they are non-metastasizing. We report four examples of a new member of this family of perivascular epithelioid cell neoplasms that occur in abdominopelvic location and show metastatic properties. The patients, all women, were aged 19 to 41 years (mean, 32), and presented with a tumor mass involving the serosa of the ileum, uterus or pelvic cavity. Morphologically, the tumors were composed of sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm and moderately pleomorphic nuclei, traversed by a delicate vasculature, mimicking clear cell carcinoma. There were areas of coagulative necrosis and occasional mitotic figures. Intracytoplasmic brown pigment was present in two cases. Spindly cells, smooth muscle and fat were absent. Lymphovascular invasion was present in all, lymph node metastasis was documented in two and metastasis to the ovary was present in one case. Two patients developed widespread metastatic disease after 10 and 28 months from diagnosis. One patient showed the clinical signs of tuberous sclerosis. In spite of the epithelial-like appearance, the tumor cells were negative for epithelial markers but were strongly positive with the melanogenesis-related marker HMB45. Another melanogenesis marker (MART-1) was positive in two cases. Other markers including S-100 protein, vimentin, muscle-specific actin, desmin and chromogranin A were negative. Thus, these tumors are not readily classifiable in the existing schema of known entities, and show overlapping morpho-phenotypic features of clear cell "sugar" tumor of the lung and epithelioid angiomyolipoma. We consider them as sarcomas composed of a pure population of uncommitted perivascular epithelioid cell, that lack modulation toward smooth muscle or adipose cells.

Comparative cytology of mucocelelike lesion and mucinous carcinoma of the breast in fine needle aspiration.

OBJECTIVE: To study the fine needle aspiration cytology (FNAC) features of mucocelelike lesion (MLL) of the breast and to compare them to those of mucinous carcinoma. STUDY DESIGN: The fine needle aspiration (FNA) smears of 7 cases of histologically proven MLL (2 malignant and 5 benign, including 4 associated with atypical ductal hyperplasia) were reviewed and compared to those of 14 mucinous carcinoma cases. RESULTS: In all cases, grossly visible thick, mucoid material was obtained from FNA. The most important features for distinguishing benign MLL from mucinous carcinoma were: (1) scant cellularity; (2) no or rare single, intact tumor cells; (3) tumor cells arranged in cohesive monolayers; and (4) absence of significant nuclear atypia. In contrast, mucinous carcinoma in general showed higher cellularity; abundant single, intact cells; three-dimensional cellular clusters in most cases; and nuclear atypia ranging from mild to severe. CONCLUSION: Mucinous lesions of the breast should be divided into MLL and frank mucinous carcinoma based on FNAC. However, FNAC diagnosis of malignant MLL has yet to be defined. Excisional biopsy is advised for all hypocellular cases for further separation into benign and malignant MLL and to rule out the possibility of hypocellular mucinous carcinoma.

Vasopressin regulates endothelin-B receptor in rat inner medullary collecting duct.

Previous studies have shown that endothelin (ET) antagonizes the actions of arginine vasopressin (AVP) in the renal collecting ducts. On the other hand, the effects of AVP on ET function within the collecting ducts of the kidney have not been investigated extensively. Using isolated inner medullary collecting ducts (IMCD), we examined the possibility that a decrease in ET(B) receptor mRNA accompanied AVP-induced downregulation of ET(B) receptors. Binding studies revealed that overnight incubation of rat IMCD cells with AVP significantly reduced the maximal binding capacity (B(max)) of ET. Activation of adenylate cyclase by forskolin decreased the total ET(B) receptor density by approximately 42% but did not affect the density of ET(A) receptors. The Rp diastereoisomer of adenosine 3', 5'-cyclic monophosphothionate, Rp-cAMPS (a specific inhibitor of protein kinase A), blocked the AVP-induced reduction in ET receptor density. Using competitive PCR method, we also observed downregulation of ET(B) receptor mRNA in IMCD treated with AVP. Additional studies were done with IMCD to determine whether AVP inhibited the ET-induced accumulation of cGMP. We saw a reduction in ET-induced cGMP accumulation when IMCD was incubated overnight with AVP. This inhibition of ET-induced accumulation of cGMP was blocked by Rp-cAMPS. These results suggest that AVP regulates ET(B) receptor expression in IMCD.

[Mucocele-like lesion of the breast-histopathology and fine needle aspiration cytology changes].

OBJECTIVE: To elucidate the histopathology and fine needle aspiration cytology (FNAC) features of mucocele-like lesion (MLL) of the breast, and to establish the criteria in separating MLL from mucinous carcinoma on the basis of pre-operative FNAC. METHODS: Seven cases of MLL (5 benign and 2 malignant) were reviewed. The histology and FNAC features were compared with 14 cases of mucinous carcinoma examined in the same period. RESULTS: All cases of MLL presented with breast lumps (1 case was detected by doctor after abnormal mammogram) and MLL patients are much younger (mean age 34.8 years for MLL and 67.9 years for mucinous carcinoma). Histologically, MLL are characterized by mucinous cysts which may rupture and discharge their contents into the surrounding tissue. The lining epithelium is bland and epithelial cells are rare in the mucin pool. Malignant MLL shows associated in-situ carcinoma. In contrast, mucinous carcinoma is formed by large mucin pools devoid of lining epithelium and contains mumerous tumor cells in the mucin pools. In all cases, grossly visible jelly-like mucous was obtained from FNA. Cytologically, all smears showed abundant mucous in the background. The most important fratures distinguishing benign MLL from mucinous carcinoma were scant cellularity, rare intact single tumor cell and tumor cells arranged in cohesive monolayered clusters lacking significant nuclear atypia. CONCLUSION: Mucinous lesions of the breast can be divided into MLL and mucinous carcinoma based on the FNAC changes. Operative therapy can be performed for definite cases of mucinous carcinoma without further biopsy. However, excisional biopsy is advised in MLL for further separation into benign and malignant categories.

Renal hypersensitivity to vasopressin in congestive heart failure.

Plasma vasopressin (AVP) levels are often elevated in congestive heart failure (CHF). To determine the significance of AVP in CHF, we performed clearance studies on the UM-X7.1 strain of cardiomyopathic (CM) hamsters with moderate heart failure and age-matched healthy controls. Exogenous AVP or a selective V2 agonist (0.3 ng.kg-1. min-1) reduced the fractional excretion of sodium (FENa) and water (FEH2O) by 40-46% in the control group. Although the CM hamsters exhibited a blunted physiological response to the V2 agonist, their urinary cAMP levels were fivefold that of normal and reflect an altered regulation of V2 receptor signalling during CHF. Additional studies also showed that infusion of a V2 antagonist (0.3 ng.kg-1. min-1) produced natriuresis and diuresis in CM hamsters (FENa: 7.9 +/- 1.1 vs. 4.8 +/- 0.6%, p < 0.05; FEH2O: 2.2 +/- 3 vs. 1.5 +/- 0. 2%, p < 0.05) but did not decrease fluid reabsorption in the normal hamsters. In conclusion, the attenuated renal response to exogenous AVP in CM hamsters may be attributed to an enhanced endogenous AVP response during CHF.

Downregulation of endothelin B receptors in cardiomyopathic hamsters.

The mechanisms responsible for abnormal fluid retention in congestive heart failure (CHF) are unclear. Studies were conducted to elucidate how endothelin (ET) may contribute to salt and water retention. Cardiomyopathic (CM) hamsters with moderate heart failure were employed for in vivo and in vitro trials. Clearance methods were used to compare the level of renal function in CM hamsters and control animals. Radioligand binding studies were also performed to determine ET receptor distribution in the inner medullary collecting ducts. CM hamsters exhibited an attenuated response to ANF infusion (FENa: 2.7 +/- 0.5 vs. 5.9 +/- 0.8%, p < 0.01; FEH2O: 1.7 +/- 0.3 vs. 3.2 +/- 0.4%, p < 0.01; UcGMP: 11.2 +/- 2.3 vs. 16.6 +/- 2.0 pmol/min, p < 0.05) and a decrease in total ET receptor density (532 +/- 77 vs. 959 +/- 154 fmol/mg protein, p < 0.005). Particularly ETB receptors were significantly reduced (214 +/- 26 vs. 483 +/- 88 fmol/mg protein, p < 0.003). Enalapril therapy simultaneously restored the natriuretic and diuretic effects of ANF and ET receptor density in the diseased animals. These studies suggest that the renin-angiotensin-aldosterone system and ET hormonal system act together, via ETB receptor downregulation, to promote the abnormal fluid retention observed in CHF.

Effect of progesterone therapy on arginine vasopressin and atrial natriuretic factor in premenstrual syndrome.

OBJECTIVES: To explore the possible role of natriuretic peptides and vasopressin in luteal phase fluid retention in premenstrual syndrome (PMS) and to determine the effect of progesterone therapy on these hormones. DESIGN: Self-controlled prospective study. SETTING: University-based medical research centre. PATIENTS: Six patients with PMS were studied during the symptomatic luteal and asymptomatic follicular phases. The follicular phase response was used as the control for each subject. INTERVENTIONS: An intravenous infusion of 3% saline solution was administered on an early follicular and a late luteal phase day in 2 menstrual cycles. Progesterone was administered orally during the second luteal phase. OUTCOME MEASURES: Osmolality, arginine vasopressin (AVP), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP) levels in plasma, osmolality, sodium, potassium, cyclic adenosine monophosphate (cAMP) and cyclic guanosine 5'-phosphate (cGMP) concentrations in urine, and thirst sensation. RESULTS: Mean basal plasma ANF and osmolality levels and the threshold for AVP release and thirst were lower, and mean urinary cyclic nucleotide levels and AVP sensitivity (amount of AVP secreted per unit rise in plasma osmolality) were higher, in the luteal phase than in the follicular phase. With saline loading, there was an increase in plasma osmolality, AVP and ANF and in urinary sodium and cyclic nucleotide levels. Plasma ANF and osmolality levels remained lower in the luteal phase compared with the follicular phase, but AVP levels at the end of the saline infusion were higher in the luteal phase than in the follicular phase. Progesterone therapy caused an increase in plasma ANF and osmolality levels and the AVP threshold and a decrease in AVP levels and sensitivity and urinary cyclic nucleotide levels. BNP levels did not change with phase or treatment. The differences in AVP threshold with phase and treatment were statistically significant (p < 0.001). There was a significant phase effect for plasma ANF (p = 0.02) and a significant or near-significant interaction effect of phase and treatment for plasma ANF (p = 0.06) and urinary cAMP (p = 0.047) and cGMP (p = 0.066). The effect of phase and treatment was not significant for the other measurements. CONCLUSIONS: Luteal phase fluid retention may be due to a relative deficiency of ANF and a lower threshold for AVP release. The symptomatic improvement produced by progesterone treatment may be due to its stimulation of ANF and inhibition of AVP release or synthesis.

Plasma and cardiac tissue atrial and brain natriuretic peptides in experimental heart failure.

OBJECTIVES: This study evaluated the role of changes in heart rate, cardiac filling pressures and cardiac tissue atrial and brain natriuretic peptides in the modulation of their plasma levels in a model of heart failure. BACKGROUND: Atrial and brain natriuretic peptides constitute a dual natriuretic peptide system that regulates circulatory homeostasis. METHODS: The effects of 1) acute ventricular pacing, 2) acute volume expansion, and 3) volume expansion after 1 week of continuous pacing on plasma atrial and brain natriuretic peptide levels were compared in eight dogs. Atrial and ventricular tissue levels of the peptides were examined in 5 normal dogs (control group), 21 dogs paced for 1 week (group 1) and 10 dogs paced for 3 weeks (group 2). RESULTS: Both acute pacing and volume expansion increased plasma atrial natriuretic peptide levels (from 53 +/- 41 to 263 +/- 143 pg/ml [mean +/- SD], p < 0.01, and from 38 +/- 23 to 405 +/- 221 pg/ml, p < 0.001, respectively). After 1 week, there was a marked increase in plasma levels of atrial natriuretic peptide, but the level did not increase further with volume expansion (from 535 +/- 144 to 448 +/- 140 pg/ml, p = 0.72). By contrast, plasma brain natriuretic peptide levels increased only modestly with acute pacing (from 12 +/- 4 to 20 +/- 8 pg/ml, p < 0.05) and after pacing for 1 week (from 13 +/- 4 to 48 +/- 20 pg/ml, p < 0.05) but did not change with acute or repeat volume expansion. In groups 1 and 2, atrial tissue levels of atrial natriuretic peptide (1.9 +/- 1.3 and 2.0 +/- 0.9 ng/mg, respectively) were lower than those in the control group (11.7 +/- 6.8 ng/mg, both p < 0.001), whereas ventricular levels were similar to those in the control group. Atrial tissue brain natriuretic peptide levels in groups 1 and 2 were similar to those in the control group. However, ventricular levels in group 2 (0.018 +/- 0.006 ng/mg) were increased compared with those in the control group (0.013 +/- 0.006 ng/mg, p < 0.05) and in group 1 (0.011 +/- 0.006 ng/mg, p < 0.05). CONCLUSIONS: Atrial and brain natriuretic peptides respond differently to changes in heart rate and atrial pressures. Reduced atrial tissue atrial natriuretic peptide levels in heart failure may indicate reduced storage after enhanced cardiac release. However, the relatively modest change in cardiac tissue brain natriuretic peptide levels suggests that the elevated plasma levels may be mediated by mechanisms other than increased atrial pressures.

Downregulation of atrial natriuretic factor clearance receptors in experimental chronic renal failure rats.

Studies were performed to examine the changes of renal ANF second messenger guanosine 3',5'-cyclic monophosphate (cGMP) responses and receptor properties in chronic renal failure (CRF). Five-sixths-nephrectomized and sham-operated Wistar rats were used. The glomerular filtration rate was decreased in the five-sixths-nephrectomized rats, which also had significantly higher plasma blood urea nitrogen and plasma atrial natriuretic factor (ANF) levels (148.5 +/- 10.2 vs. 115.7 +/- 7.3 pg/ml, P = 0.01) than the sham rats. In vitro ANF-stimulated cGMP accumulations in glomeruli of five-sixths-nephrectomized rats were higher than controls. Radioligand-binding experiments showed downregulation of the total ANF receptor in both acid and nonacid wash CRF glomeruli (nonacid wash: 189 +/- 25 vs. 362.8 +/- 52.8 fmol/mg protein, P < 0.05; acid wash: 449.8 +/- 67 vs. 652.7 +/- 52.5 fmol/mg protein, P < 0.05). No change in receptor densities was observed in the des(Gln18,Ser19,Gly20,Leu21)atrial natriuretic peptide-(4--23)-NH2-resistant receptors between sham and CRF rat glomeruli. Therefore, downregulation of ANF clearance receptors exists in CRF rat glomeruli, and this is associated with the exaggerated ANF-stimulated cGMP response in these CRF glomeruli. Hypersensitivity of CRF rat to ANF, together with high plasma ANF levels and downregulation of clearance receptor, may contribute to increased sodium excretion in CRF.

In vitro hormone-stimulated atrial natriuretic factor release is increased in experimental renal failure.

The effects of hormone stimulation on atrial natriuretic factor (ANF) release in atria were studied in experimental renal failure rats. In vitro experiments were done in two groups of male Wistar rats. Group 1 rats were sham operated, and group 2 rats were subjected to 5/6 nephrectomy. Overall glomerular filtration rate was significantly reduced (1.98 +/- 0.10 vs. 0.75 +/- 0.05 ml/min, p < 0.001) in nephrectomized rats. These rats were also mildly uremic [blood urea nitrogen (BUN): 18 +/- 0.6 vs. 60 +/- 3.9 mg/dl p < 0.001]. The right atria of partially nephrectomized and sham-operated rats were isolated and perfused in a modified Langendorff apparatus to measure ANF release rate. Experiments were done in two phases. In the initial phase, spontaneous release of ANF was measured. In the second phase, angiotensin II (10(-6) M), vasopressin (10(-6) M) or endothelin (ET 1; 10(-6) M) were added into the perfusate. Spontaneous ANF release by the atria of renal failure rats was significantly elevated compared to intact rats. A significant positive correlation was found between ANF release rate and BUN (r = 0.65, p < 0.01). This suggests that the increase in ANF release by the atria of chronic renal failure (CRF) rats is related to the severity of renal impairment. Angiotensin II, vasopressin and endothelin induced exaggerated increases in ANF release by the atria of CRF rats. These results show that a shift in stimulus response curve is present and can contribute to the observed increase in plasma ANF levels in CRF rats.

Cyclic guanosine monophosphate responses to atrial natriuretic factor, brain natriuretic peptide, but not C-type natriuretic peptide, and the characterization of their receptors in rat medullary thick ascending limb.

The effects of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on renal medullary thick ascending limb (mTAL) have not been fully understood. The aim of this study is to examine the second-messenger responses of rat mTAL to ANF, BNP, and CNP. Characterizations of the ANF, BNP, and CNP receptors in mTAL were also performed by radioligand studies. Results showed that ANF and BNP were both capable of eliciting cyclic guanosine monophosphate (cGMP) responses in mTAL. Conversely, no cGMP response was observed upon stimulation by CNP in mTAL. The presence of ANF receptors was demonstrated by radioligand studies. One receptor site was found, and the Kd and maximum binding capacity were 4.0 +/- 0.45 nmol/L and 277.8 +/- 47.7 fmol/mg protein, respectively. BNP receptors were also found in mTAL, and ANF and BNP were sharing the same receptor. On the contrary, no CNP receptor could be shown by radioligand studies. These results suggest that guanylyl cyclase-coupled receptors (atrial natriuretic peptide receptor-A [ANPR-A]) specific for ANF and BNP are present in rat mTAL, while those for CNP (ANPR-B) are absent. ANF and BNP but not CNP act on mTAL to control water excretion.

Second messenger changes of atrial natriuretic factor and brain natriuretic peptide in kidneys of cardiomyopathic hamsters.

The effects of natriuretic peptides in kidney are blunted in congestive heart failure (CHF). The aim of this study is to examine the changes of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) second messenger productions in CHF. Experiments were conducted on 300-day-old normal and cardiomyopathic hamsters. Blood was collected for ANF measurement. cGMP accumulation studies were done in glomeruli upon ANF and BNP stimulation, and in inner medullary collecting duct (IMCD) cells upon ANF stimulation. Higher plasma ANF levels were found in cardiomyopathic hamsters (811.3 +/- 124.6 vs. 166.6 +/- 13 pg/ml, p < 0.01). ANF-stimulated cGMP accumulations in glomeruli and IMCD cells were higher in cardiomyopathic hamsters. Increased BNP-stimulated cGMP accumulations were also observed in cardiomyopathic hamster glomeruli. These results suggest that the renal hyporesponsiveness to natriuretic peptides in CHF in not due to attenuated ANF and BNP second messenger productions.

Absence of C-type natriuretic peptide receptors in hamster glomeruli.

The distribution of atrial natriuretic peptide receptor B (ANPR-B) varies between tissues and species. The aim of this study is to determine whether ANPR-B is present in the hamster glomeruli. In vitro C-type natriuretic peptide (CNP)- and atrial natriuretic factor (ANF)-stimulated cGMP accumulation studies were performed in hamster glomeruli. Elevated cGMP accumulations were observed upon ANF addition. No cGMP response was seen with CNP. Competitive receptor-binding experiments were performed with 125I-CNP and 125I-ANF against their respective cold peptides in hamster glomeruli. Although no CNP binding was detected, positive ANF binding was found and two types of ANF receptor were demonstrated. The affinity (Kdl) and maximum binding capacity (Bmaxl) of the high-affinity ANF receptor were 0.014 +/- 0.001 nM and 60.4 +/- 10.2 fmol/mg protein, respectively. Those of the low-affinity receptor (Kd2 and Bmax2) were 45.7 +/- 6.2 nM and 28.3 +/- 6.3 pmol/mg protein, respectively. Similarly, saturation binding experiments also failed to show any CNP receptor binding in hamster glomeruli. This finding suggests that ANPR-B is not present in hamster glomeruli and CNP is not a direct physiological regulator of hamster renal function.

Review of continuous sutures in dermatologic surgery.

BACKGROUND: Continuous sutures have been developed to close surgical defects to save time, to distribute tension evenly, or to improve the cosmetic result. The choice of suture technique can significantly affect the speed of closure and the eventual appearance of the scar. OBJECTIVE: To review the different types of continuous sutures, their advantages, and disadvantages. CONCLUSION: Recommendations are made regarding the appropriate use of continuous sutures in wounds depending on the amount of tension in the wound, and requirement of a good cosmetic result.

Dual natriuretic peptide system in experimental heart failure.

OBJECTIVES: The objectives of this study were 1) to define in an experimental model of heart failure the time course of changes in plasma brain natriuretic peptide concentrations during the development of and recovery from heart failure, and 2) to relate the changes to changes in atrial natriuretic peptide concentration and hemodynamic status. BACKGROUND: Brain natriuretic peptide is a circulating peptide with homology to atrial natriuretic peptide. However, unlike the latter, its changes during heart failure and its relation to cardiac filling pressures have not been studied. METHODS: Eight male mongrel dogs underwent right ventricular pacing at 250 beats/min for 3 weeks until heart failure occurred and were followed up during recovery for 4 weeks after cessation of pacing. RESULTS: Heart failure was characterized by an increase in both left ventricular and end-diastolic pressure (6.6 +/- 4.1 mm Hg at the control measurements to 35.1 +/- 5.9 mm Hg at 3 weeks, p < 0.01) and right atrial pressure (6.7 +/- 1.1 to 11.4 +/- 2.1 mm Hg, p < 0.01). Recovery was accompanied by a return of cardiac filling pressures to control level. The time course of change of arterial plasma brain natriuretic peptide concentration was similar to that of atrial natriuretic peptide. Plasma concentrations of both peptides increased after 1 week of pacing (16 +/- 4 pg/ml at the control measurement to 59 +/- 20 pg/ml at 1 week, p < 0.001 for brain natriuretic peptide and 84 +/- 55 to 856 +/- 295 pg/ml, p < 0.001 for atrial natriuretic peptide). The level of both peptides then stayed level with no further increase at 3 weeks and returned to the control value by 4 weeks of recovery. There was an excellent correlation between plasma concentrations of the two peptides (r = 0.86, p < 0.001) and between the two peptides and cardiac filling pressures. However, compared with atrial natriuretic peptide, plasma brain natriuretic peptide concentration had a smaller percent increase during evolving heart failure and a slower rate of decline at recovery. CONCLUSIONS: Brain and atrial natriuretic peptide constitute a dual natriuretic system and are both responsive to changes in cardiac filling pressures in heart failure. However, brain natriuretic peptide appears to be less responsive than atrial natriuretic peptide.

The running locked intradermal suture. A cosmetically elegant continuous suture for wounds under light tension.

A new suture technique, the running locked intradermal suture, is introduced. The suture is continuous and buried, and is designed for closing simple elliptical wounds under light tension in which a good cosmetic result is desired. It is used in conjunction with a topical antibiotic and a transparent dressing. This technique reduces the dermal dead space, achieves close approximation of the epidermal wound edges, has a good cosmetic appearance soon after surgery, reduces necessary postoperative wound care, reduces the risk of wound infection in clean surgical wounds, and obviates suture removal. Three examples of its application on the face are presented. It is compared with frequently used standard wound closure methods are discussed.