Hypoestoxide, a novel anti-inflammatory natural diterpene, inhibits the activity of IkappaB kinase.

Most inflammatory agents activate nuclear factor-kappaB (NF-kappaB), resulting in induction of genes coding for cytokines, chemokines, and enzymes involved in amplification and perpetuation of inflammation. Hypoestoxide (a bicyclo [9,3,1] pentadecane) is a diterpene from Hypoestes rosea, a tropical shrub in the family Acanthacea, several members of which are used in folk medicine in Nigeria. Here, we demonstrate that hypoestoxide (HE) abrogates the production of pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) in lipopolysaccharide (LPS)-activated normal human peripheral blood mononuclear cells. Moreover, HE inhibits the production of nitric oxide (NO) by IL-1beta- or IL-17-stimulated normal human chondrocytes. In vivo, oral administration of HE to mice significantly ameliorated hind paw edema induced by antibodies to type II collagen plus LPS. Furthermore, topical administration of HE to mice also significantly inhibited phorbol ester-induced ear inflammation. The anti-inflammatory activity of HE may be due in part to its ability to inhibit NF-kappaB activation through direct inhibition of IkappaB kinase (IKK) activity. Thus, HE could be useful in treating various inflammatory diseases and may represent a prototype of a novel class of IKK inhibitors.

Morphometric studies of cystic and tubulointerstitial kidney diseases with hepatic fibrosis in children.

Portal tract fibrosis with biliary ductular enlargement or proliferation occurs in a number of genetic diseases that have cystic or tubulointerstitial renal lesions. These include some with renal cystic disease such as autosomal recessive diseases (e.g., infantile polycystic disease, juvenile polycystic disease, and Meckel's syndrome), autosomal dominant diseases (e.g., adult polycystic disease) and, rarely, tuberose sclerosis and dominant glomerulocystic disease. Portal tract fibrosis with biliary enlargement and proliferation occurs also with tubulointerstitial kidney diseases. These probably include at least three disorders in the category nephronophthisis-congenital hepatic fibrosis (one autosomal recessive disease and two either autosomal or X-linked recessive diseases) plus Jeune's syndrome (the tubulointerstitial diseases Fanconi's familial nephronophthisis and anti-tubular membrane antibody disease do not regularly cause hepatic fibrosis). Morphometric data on ratios of bile ductules to connective tissue in hepatic portal tracts show high values for infantile polycystic disease (mean, 0.616) compared to lower values for juvenile polycystic disease (mean, 0.286). That the cystic renal lesions of the first two diseases differ in type and time course is known. Similar data on ratios of glomeruli plus tubules to connective tissue in renal cortices and of tubules to connective tissue in outer medullary zones of kidneys, respectively, are as follows: for Fanconi's nephronophthisis, 0.445 and 0.197; for anti-tubular basement membrane antibody disease, 0.585 and 0.164; and for the three types of nephronophthisis-congenital hepatic fibrosis studied, 0.668 and 0.446, 1.39 and 0.921, and 1.18 and 0.12. These data support clinical impressions that the category nephrophthisis-congenital hepatic fibrosis includes more than one disease entity.

Biochemical hypothyroidism in Nigerian children with nephrotic syndrome.

The nephrotic syndrome in Nigerian children is known to be largely associated with the endemicity of quartan malaria. Routine thyroid function studies were carried out on 24 children with clinical and biochemical evidence of the nephrotic syndrome. The children, aged four to 14 years, were all in the active phase of their disease, presenting with facial and pedal oedema and ascites. There was severe hypoalbuninaemia [mean (S.E.); 19.2 (1.1) g/l], hypercholesterolaemia; 10.5 (1.0) mmol/l and severe albuminuria ranging from 1 to 10 g/l. There was no clinical evidence of thyroid disease. The results of thyroid function tests in these children were compared with those of 181 apparently healthy children of the same age range. The mean total serum thyroxine levels (S.E.) were 118.3 (2.6) and 50.0 (6.4) nmol/l in controls and patients, respectively; T3 resin uptake values were 29.8 (0.2)% and 33.1 (1.2)%; the free thyroxine index (FTI) was 34.7 (0.8) and 16.7 (1.9) while thyrotropin (TSH) levels were 4.8 (0.2) and 10.6 (1.0) mU/l (IRP. MRC 68/38), respectively. The findings of low levels of thyroxine and FTI in association with high levels of TSH suggest that a state of primary hypothyroidism exists in these nephrotic children.

Retroperitoneal chondrosarcoma presenting with pleural effusion: a case report.

An adolescent male patient presented with pleural effusion of undetermined etiology which was unresponsive to antituberculous therapy. He died suddenly a few months later and was found at autopsy to have suffered from acute catastrophic pulmonary occlusion, secondary to embolization from retroperitoneal chondrosarcoma which had invaded and occluded the pulmonary arteries via the inferior vena cava. The rarity of this phenomenon in children prompted this report.