Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW/Jms

Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct.     

Hepatitis B surface antigen particles of subtypes adw and adr, and compound subtype (adwr) in symptom-free carriers in Japan.

Of sera from 1,878 Japanese blood donors who carried hepatitis B surface antigen (HBsAg), 420 were subtyped as adw (22.4%) and 1,443 as adr (76.8%); only 15 (0.8%) contained HBsAg of subtype ayw or ayr. Sera with HBsAg/adr had higher HBsAg titres than those with HBsAg/adw (geometric mean of haemagglutination titre: 10.1 +/- 2.4 vs. 9.7 +/- 2.4, p less than 0.01), and a higher prevalence of hepatitis B e antigen (24% vs. 13%, p less than 0.001). Carriers of HBsAg/adr progressively predominated over those of HBsAg/adw with increasing age. Of sera from 1,863 carriers of HBsAg/adw or HBsAg/adr, 182 (9.8%) contained HBsAg particles with both subtypic determinants in the w/r allele. The presence of w and r determinants on the same particles was ascertained by sandwiching them between monoclonal antibody with the specificity for w and that with the specificity for r. HBsAg particles of compound subtype (adwr) were found more often in sera with hepatitis B e antigen than those without it (145/403 [36.0%] vs. 37/1,460 [2.5%], p less than 0.001). Sera with HBsAg/adwr particles had HBsAg titres higher than those without them (12.4 +/- 1.9 vs. 9.7 +/- 2.3, p less than 0.001). HBsAg/adwr particles arise from phenotypic mixing of the S-gene product of wild-type virus and that of mutants with point mutations for subtypic changes. The results obtained indicated that HBV strains of subtype adr have a higher replicative activity than those of adw, and suggested that mutations in the S gene for subtypic changes would be associated with an active replication of hepatitis B virus.     

IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response

IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1alpha and IL-1beta, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by T(h)2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response (AHR) in IL-1alpha/beta-deficient (IL-1alpha/beta(-/-)) mice was significantly reduced from the levels seen in wild-type mice, whereas the responses seen in IL-1Ra(-/-) mice were profoundly exacerbated, suggesting that IL-1 is required for T(h)2 cell activation during AHR. OVA-specific T cell proliferation, IL-4 and IL-5 production by T cells, and IgG1 and IgE production by B cells in IL-1alpha/beta(-/-) mice were markedly reduced compared with these responses in wild-type mice; such responses were enhanced in IL-1Ra(-/-) mice. Using IL-1alpha(-/-) and IL-1beta(-/-) mice, we determined that both IL-1alpha and IL-1beta are involved in this reaction. Both IgG1 and IgE levels were reduced in IL-1beta(-/-) mice, while only IgE levels were affected in IL-1alpha(-/-) mice, indicating a functional difference between IL-1alpha and IL-1beta. These observations indicate that IL-1 plays important roles in the development of AHR.     

Strain combination-dependent genesis of necrotizing arteritis in anti-ICAM-1 antibody-perfused renal allografts in the rat

Rat kidneys were perfused with anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibody prior to allo-transplantation. In the two strain combinations examined, LEJ-to-WKAH transplants resulted in accelerated graft loss, and no prolongation of graft survival. The accelerated graft logs was the resut of frequent occurrence of necrotizing arterttis wlthln the grafts. In contrast, TO-to-WKAH transplants resulted in no change In graft survival and no arteritis. Necratidng vasculitis in the LEJ-to-WKAH grafts was characterlzed by flbrinoid necrosis, collection of cellular infiltrates and serum macromolecular protein entrapment. The F(ab')² form of anti-ICAM-1 antlbody partially preserved the antibody's capacity to accelerate graft loss. Therefore, although endothelial injury by Fc-mediated cytotoxicity may be involved in vascular damage, other mechanisms also come into play. The amount and distribution pattern of ICAM-1 antigen were identical in both TO and LEJ strains. Intravenous anti-CAM-1 antibody administration combined with lipopolysaccharide, Poly(1)-Poly(C), warm ischemia to the kidney, or subcutaneous immunization with allogeneic spleen cells, but without renal transplantation, did not generate necrotizing vasculitis or proteinuria. These observations plus our previous data on the rat liver transplantation model clearly show that graft perfusion with anti-ICAM-1 monoclonal antibody invokes extensive vascular damage within allografts by Fc-mediated and Fc-independent mechanisms, depending on the donor-to-host combination.     

A Consideration on the new classification of latest lung ventilators

Concerning the classification of ventilators, Elam (1958), Faireley (1959), and Hunter (1961) reported some simple ones such as pressure limited, volume limited, pressure preset, or volume preset models. Mapleson (1969) also classified them by the generating force or cycling together with the above-mentioned types.The latest ventilators applicable to patients with respiratory failure usually have some cut-off function at high airway pressures as a safety measure. Therefore, all of them belong to the pressure limited type. Some ventilators are of two types such as the time cycled and pressure cycled type.Therefore, we attempted to classify ventilators into four groups, i.e. the time cycled, volume cycled, pressure cycled and selective time-pressure cycled types according to the fundamental mode of ventilator function, the so-called change of cycling from inspiration to expiration. Each group was further divided into subgroups according to preset dials such as respiratory rate, I/E ratio, inspiration time, expiration time, tidal volume, flow rate and airway pressure.By this method, fifty one ventilators on the market in Japan can be classified without overlapping. Although this classification seems complex, it will be of use in selecting ventilators by emphasizing preset dials according to the users needs, ability or both.(Goto Y, Takahashi K, Harada J et al.: A consideration on the new classification of latest lung ventilators. J Anesth 1: 178–182, 1987)     

Pharmacologic properties of candesartan cilexetil--possible mechanisms of long-acting antihypertensive action

Candesartan cilexetil has shown potent and long-lasting antihypertensive effects in clinical trials and in several animal models of hypertension. In spontaneously hypertensive rats, the duration of the antihypertensive effect of candesartan cilexetil was compared to those of losartan, valsartan, eprosartan, and irbesartan at the same degree of maximal blood pressure reduction. A single oral dose of candesartan cilexetil at 0.3 mg/kg reduced maximal blood pressure by about 25 mm Hg, and the antihypertensive effect of candesartan cilexetil lasted the longest, continuing for more than 1 week, without an effect on circadian rhythm. In a rabbit aortic preparation, candesartan, active form of candesartan cilexetil, decreased the maximal contractile response of angiotensin II. This inhibitory mode was different from that of other angiotensin II-receptor antagonists, and showed a shift to the right in the angiotensin II-induced contraction curve and/or a small depression of the maximal response. In kinetic studies using bovine adrenal cortical membrane and tritiated candesartan, both receptor association and dissociation were found to be slow. The dissociation rate of tritiated candesartan binding (t1/2 = 66 min) was five times slower than that of radiolabelled angiotensin II binding (t1/2 = 12 min). The insurmountable inhibition of candesartan in vascular contraction is the result of its tight binding and slow dissociation from angiotensin II AT1 receptors. These characteristics are related to the potency and long duration of action in candesartan cilexetil.     

The anti-inflammatory secoiridoid glycosides from Gentianae Scabrae Radix: the root and rhizome of Gentiana scabra

Journal of Natural Medicines - Gentianae Scabrae Radix is a well-known traditional medicine that is used for the treatment of hepatitis, cholecystitis and inflammatory diseases. It consists mainly...