Dietary supplementation of clinically utilized PI3K p110α inhibitor extends the lifespan of male and female mice.

Diminished insulin and insulin-like growth factor-1 signaling extends the lifespan of invertebrates1-4; however, whether it is a feasible longevity target in mammals is less clear5-12. Clinically utilized therapeutics that target this pathway, such as small-molecule inhibitors of phosphoinositide 3-kinase p110α (PI3Ki), provide a translatable approach to studying the impact of these pathways on aging. Here, we provide evidence that dietary supplementation with the PI3Ki alpelisib from middle age extends the median and maximal lifespan of mice, an effect that was more pronounced in females. While long-term PI3Ki treatment was well tolerated and led to greater strength and balance, negative impacts on common human aging markers, including reductions in bone mass and mild hyperglycemia, were also evident. These results suggest that while pharmacological suppression of insulin receptor (IR)/insulin-like growth factor receptor (IGFR) targets could represent a promising approach to delaying some aspects of aging, caution should be taken in translation to humans.

Neuro-Behçet's disease presenting with tumour-like lesions and responding to rituximab.

We describe a patient with neuro-Behçets disease (NBD) that presented with symptoms of raised intracranial pressure including papilloedema. MRI revealed tumour-like lesions which, on biopsy, confirmed an active vasculitis. Treatment was commenced with prednisone and cyclophosphamide which proved unsuccessful with enlargement of the cerebral mass lesions. Infliximab and mycophenolate were trialled also without benefit. The patient required ventriculoperitoneal shunts to relieve the symptoms of hydrocephalus. Rituximab was then commenced with significant symptomatic and imaging improvement. The case is unique, in our experience, in the need for shunting to relieve the symptoms of hydrocephalus related to vasculitis.

[Ethylene-1,2-bis(diphenylphosphine)-P,P']dinitratoplatinum(II) and cis-bis[(diphenylphosphinomethyl)-diphenylphosphine oxide-O,P]-platinum (II) dinitrate dihydrate.

In [Pt(dppe)(NO(3))(2)], where dppe is ethylene-1,2-bis(diphenylphosphine) (C(26)H(24)P(2)), the Pt atom is coordinated by the two P atoms and by two O atoms of the two nitrate ions. The molecule has a distorted square-planar geometry, with one of the nitrate groups directed on each side of the plane. The cation in cis-[Pt(dppmO-O,P)(2)](NO(3))(2) x 2H(2)O, where dppmO is bis(diphenylphosphinomethyl)diphenylphosphine oxide (C(25)H(22)OP(2)), comprises two five-membered chelate rings, each dppmO ligand being coordinated to platinum through one P atom and the O atom. The larger P--Pt--P angle of 102.25 (4) degrees is due to steric interactions between the two phenyl groups on each P atom.

Gastro-intestinal Kaposi's sarcoma, with special reference to the appendix.

Kaposi's sarcoma (KS) of the gastro-intestinal tract is a common disease in the AIDS setting, although it is often asymptomatic. In this paper we wish to highlight the occurrence of gastro-intestinal KS with appendiceal involvement. Two of the patients presented with features of acute appendicitis, and KS of the appendix was not suspected at the time of surgery. In the remaining patient KS of the appendix was part of generalised gastro-intestinal involvement. It is important to remember that KS can cause appendicitis by producing a submucosal nodule that abuts into the lumen and thereby causes obstruction. KS of the gastro-intestinal tract may therefore masquerade as 'simple' appendicitis, or indeed remain asymptomatic.

Threshold effect of liver iron content on hepatic inflammation and fibrosis in hepatitis B and C.

BACKGROUND/AIMS: In hepatitis C, iron depletion may improve serum aminotransferases and the response to interferon, but it is not known whether inflammation and fibrosis correlate with hepatic iron content. Our aim was to establish whether hepatic iron content correlates with histological and serum indices of hepatic inflammation and fibrosis in hepatitis B and C. METHODS: Total hepatic iron was measured using computerized histomorphometry, and hepatic inflammation and fibrosis using a modified Knodell score, on histological slides from 31 patients with chronic hepatitis B and 38 with hepatitis C. RESULTS: Total hepatic iron was similar in the hepatitis B and C groups (0.82 +/- 1.72% and 0.56 +/- 1.12%; mean +/- SD). No iron was detectable in 11 patients with hepatitis B and 13 with hepatitis C. Alanine aminotransferase (85.96 +/- 67.1 vs 44.2 +/- 39.7 p < 0.05), aspartate aminotransferase (93.8 +/- 75.6 vs 47 +/- 33.5 IU/ml p < 0.05) and histological inflammatory score (9.33 +/- 3.51 vs 7.79 +/- 3.3 p = 0.07) were increased in those with stainable hepatic iron compared to those without. However, where iron was present, no association was found between the amount of hepatic iron and inflammatory or fibrosis scores. In hepatitis C, fibrosis was minimal in 77% of patients if iron was absent vs 24% with iron present, while marked fibrosis was present in 56% with iron vs 15% without iron (p < 0.01, Fisher's exact test). CONCLUSION: Hepatic iron is associated with increased hepatic inflammation in chronic hepatitis B and hepatitis C and with high fibrosis scores in hepatitis C. There is a threshold effect, and once present, increasing iron does not correlate with increasing inflammation or fibrosis.

Massive gastro-intestinal haemorrhage due to vascular ectasia of the duodenum. A case report.

Vascular ectasia of the duodenum as an unusual source of upper gastro-intestinal bleeding in a patient with cirrhotic portal hypertension and oesophageal varices is reported. Morphological structure and situation of ectatic duodenal vessels indicate the possible coexistence of variceal distension and angiodysplasia.