Mechanism of atrial natriuretic polypeptide and sodium nitroprusside-induced relaxation in guinea-pig tracheal smooth muscle

Atrial natriuretic polypeptide (ANP) is composed of a family of peptides isolated from rat and human atria. In the present study, the relaxant effects of ANP, sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate (GMP) were investigated in guinea-pig tracheal smooth muscle, and the tissue cyclic GMP and cyclic adenosine monophosphate (AMP) concentrations were measured. ANP, sodium nitroprusside and 8-bromo-cyclic GMP showed relaxant effects on the spontaneous tone in normal Krebs solution (5.9 mmol/l K(+)-2.4 mmol/l Ca++ solution). They diminished relaxant effects on 40 mmol/l K(+)-0.1 mmol/l Ca++ induced contraction, which was approximately the same tension as the spontaneous tone. Sodium nitroprusside and 8-bromo-cyclic GMP diminished less relaxant effects on 40 mmol/l K(+)-2.4 mmol/l Ca++ induced contraction, but ANP showed no relaxation. The tissue cyclic GMP levels following administration of ANP and sodium nitroprusside in normal Krebs solution, in 40 mmol/l K(+)-2.4 mmol/l Ca++ solution, and in 40 mmol/l K(+)-0.1 mmol/l Ca++ solution increased dose-dependently without regard to external Ca++ concentrations, while the tissue cyclic AMP levels did not change. These results suggest that ANP might be a novel potent relaxant in airway smooth muscle and the relaxant effect may be, at least in part, mediated by cyclic GMP. There was a difference in relaxant effects on tracheal smooth muscle between ANP and sodium nitroprusside.     

β2-glycoprotein I, anti-β2-glycoprotein I, and fibrinolysis

β₂-glycoprotein-I (β₂GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. β₂GPI has been known as a natural anticoagulant regulator. β₂GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, β₂GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, β₂GPI may contribute to thrombin generation in vivo. Phospholipid-bound β₂GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-β₂GPI antibodies increases the affinity of β₂GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of β₂GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-β₂GPI antibodies with β₂GPI also decreased fibrinolytic activity in this assay system. β₂GPI is proteolytically cleaved by plasmin in domain V (nicked β₂GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked β₂GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked β₂GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop.     

Carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine in rats administered bis(2-hydroxypropyl)amine and sodium nitrite

The carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine(BHP) was investigated in male Wistar rats administered bis(2-hydroxypropyl)amine(BHPA) mixed in powder diet at a concentration of 1%, and sodiumnitrite (SN) dissolved in distilled water at concentrationsof 0.15 and 0.3%, for 94 weeks. Urinary excretion of BHP wasdetected in rats given 1% BHPA and 0.3% SN but not in the groupsreceiving either of these precursors alone. Nasal cavity, lung,esophagus, liver and urinary bladder tumors were found in animalstreated with combinations of 1% BHPA and 0.15 or 0.3% SN, suggestingthat the target organs of the endogenously synthesized BHP aresimilar to those affected when the carcinogen is administeredexogenously. The incidences of nasal cavity and lung tumorsreached 74 and 58% in rats given 1% BHPA and 0.3% SN, respectively.Tumors at sites other than target organs were only found atlevels similar to those previously reported for spontaneoustumors in male Wistars. The present results clearly indicatedthe tumor inducibility of a nhrosatable amine, BHA, throughan endogenous nitrosation by feeding to rats in conjunctionwith nitrite, and provide further suggestive evidence that endogenousnitrosations of environmental nitrosatable amines can be a potentialrisk factor in human cancer development.     

Langerhans Cell Histiocytosis Presenting as a Varicelliform Eruption over the Entire Skin

A boy with skin eruptions resembling varicella and specific for Langerhans cell histiocytosis (LCH) is reported. At his initial visit when he was four months old, vesiculopustular lesions were present over the entire body; these had first appeared on the third day post partus. Histopathological, immunohistochemical, and electron microscopical examination confirmed the Langerhans cell phenotype and Birbeck granules in the responsible cells. He also had hydronephrosis, recurrent fever, and cutaneous bacterial infections. His parents refused further medical treatment and he died of diarrhea with cachexia about two years later. LCH may present diagnostic difficulties by manifesting as a skin eruption which resembles varicella.     

Diuretic and hypotensive actions of torasemide in hypertensive models of rat

The diuretic and the antihypertensive actions of torasemide were examined in renal and genetic hypertensive rats and compared to the effects of furosemide. Oral administration of torasemide (1 and 3 mg/kg) elicited a dose-dependent increase in the excretion of urine and electrolytes and elevated the urinary Na/K ratio in both renal and genetic hypertensive rats. Torasemide and furosemide had a similar maximum diuretic effect in the normotensive Wistar rat and the spontaneously hypertensive rat (SHR). However, the diuretic activity of furosemide was weaker in the renal hypertensive rat (RHR). Torasemide showed approximately 30 times greater diuretic potency than furosemide. Torasemide and furosemide demonstrated hypotensive action in hypertensive rat models, but not in the normotensive Wistar rat. Especially in the RHR, torasemide exhibited a more potent hypotensive action than furosemide. These results show that the diuretic and antihypertensive activities of torasemide are effective in various rat models of hypertension, while the diuretic activity of furosemide is weak in certain hypertensive rat models. © 1992 Wiley-Liss, Inc.     

LAPAROSCOPIC TREATMENT FOR PERFORATED APPENDICITIS WITH PELVIC ABSCESS

We performed laparoscopic appendectomy and drainage to treat panperitonitis due to perforated appendicitis that occurred in a 28‐year‐old woman. We believe this is an appropriate procedure to treat perforated appendicitis because it is safe and minimally invasive, and faster recovery can be expected than after conventional open appendectomy.