Malignant lymphoma of the head and neck

Oral Diseases (2010) 16 , 119–128 Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck area. They are classically divided into two subgroups, Hodgkin’s lymphomas (HLs) and non‐Hodgkin’s lymphomas (NHLs). We describe the clinical characteristics of head and neck lymphomas and the methods to establish the diagnosis. The World Health Organization classification of lymphoid tissues describes more than 50 different histological types, and we analyse the most common staging system for lymphomas, the Ann Arbor staging system. Finally, the different therapeutic approaches are discussed.     

Experimental evaluation of the antiulcer activity of calcium pectate

Both chronic (prophylactic) and single administration of standardized calcium pectate considerably increased the resistance of rat stomach mucous membrane with respect to ulcerogenic factors of various etiology, including immobilized stress, indomethacin, ethanol, prednizolone, and histamine, according to H. Shay's model. The gastroprotective effect of this polysaccharide was comparable with or exceeded the action of famotidine, sea buckthorn oil, and maalox.     

Induction of trefoil factor (TFF)1, TFF2 and TFF3 by hypoxia is mediated by hypoxia inducible factor-1: implications for gastric mucosal healing

Background and purpose:

Mucosal microcirculation is compromised during gastric damage induced by non-steroidal anti-inflammatory drugs, such as aspirin. Consequently, oxygen supply to epithelial cells is decreased. The trefoil factor (TFF) peptides are involved in mechanisms of defence and repair in the gastrointestinal tract but their regulation at sites of gastric injury is unknown.

Experimental approach:

Hypoxia and expression of TFF genes and peptides were measured in the damaged stomach of aspirin-treated rats. In a human gastric cell line (AGS cells), the effects of hypoxia and of hypoxia inducible factor (HIF)-1 (through transient transfection of HIF-1α siRNA or over-expression of HIF-1α) on TFF gene expression were evaluated.

Key results:

Hypoxyprobe immunostaining, up-regulation of TFF2 (1.9-fold) and TFF3 (1.8-fold) and a non-significant increase of TFF1 (1.5-fold) mRNA were observed in the damaged stomach of aspirin-treated rats, compared with control animals. Hypoxia (3% O₂, 16 h) induced mRNA for TFF1 (5.8-fold), TTF2 (9.1-fold) and TFF3 (9.3-fold) in AGS cells, an effect mediated by HIF-1, as transient transfection of HIF-1α siRNA reduced the effects of hypoxia. Over-expression of HIF-1α by transfection in non-hypoxic epithelial cells produced a similar pattern of TFF induction to that observed with hypoxia and transactivated a TFF1 reporter construct.

Conclusions and implications:

Hypoxia inducible factor-1 mediated the induction of TFF gene expression by hypoxia in gastric epithelial cells. Low oxygen levels and up-regulation of TFF gene expression in the damaged stomach of aspirin-treated rats suggest that hypoxia induced expression of TFF genes at sites of gastric injury.     

Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells

BACKGROUND AND PURPOSE

Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive.

EXPERIMENTAL APPROACH

In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 µM) on human hepatic cells.

KEY RESULTS

Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV triggered apoptosis via the intrinsic pathway. In addition, EFV directly affected mitochondrial function in a reversible manner, inducing a decrease in mitochondrial membrane potential and an increase in mitochondrial superoxide production, followed by a reduction in cellular glutathione content. The rapidity of these actions rules out any involvement of mitochondrial DNA replication, which, until now, was thought to be the main mechanism of mitochondrial toxicity of antiretroviral drugs. Importantly, we also observed an increase in mitochondrial mass, manifested as an elevated cardiolipin content and enhanced expression of mitochondrial proteins, which was not paralleled by an increase in the mtDNA/nuclear DNA copy number ratio. The toxic effect of EFV was partially reversed by antioxidant pretreatment, which suggests ROS generation is involved in this effect.

CONCLUSION AND IMPLICATIONS

Clinically relevant concentrations of EFV were shown to be mitotoxic in human hepatic cells in vitro, which may be pertinent to the understanding of the hepatotoxicity associated with this drug.     

肥胖抑素与Ghrelin

体重部分地受大脑或胃肠道合成的肽类激素的调控。Ghrelin前激素原含117个氨基酸残基，经翻译后裂解作用形成Ghrelin，由28个氨基酸组成。我们检索基因库，与另外11种哺乳动物进行Ghrelin前激素原的序列比较，除了已知的Ghrelin信号肽，我们还确定了另一保守区，侧链含有转化酶裂解部位，编码一种23个氨基酸的肽链，其C端侧翼有保守的甘氨酸残基，可能经酰胺化作用。我们称此Ghrelin相关肽为肥胖抑素（Obestatin）。     

Ascorbic acid during cerebral ischemia in newborn piglets

We measured ascorbic acid (reduced and oxidized) in brain, CSF and blood, before, during and after cerebral ischemia in newborn piglets. Bilateral carotid ligation induced a 54% decrease in cerebral blood flow (p < 0.01) and a 43% decrease in the cerebral metabolic rate of oxygen (p < 0.01). After ischemia and reperfusion, we obtained a 60% decrease (p < 0.01) in total brain ascorbic acid content. CSF ascorbic acid increased during reperfusion:+60% at 30min (p < 0.001) and +160% at 120min (p < 0.05). Blood ascorbic acid content did not change. These changes and the absence of massive oxidation of ascorbic acid in brain tissue suggest release of ascorbic acid by the brain during ischemia.     

Unilateral oophorectomy in polycystic ovary syndrome: a treatment option in highly selected cases?

We performed unilateral oophorectomy (UO) in three patients with polycystic ovary syndrome (PCOS) and long-standing infertility. The indication for performing this procedure was a combination of ovarian pathology and the long-standing infertility. All three patients were resistant to clomiphene citrate and before UO all patients had been treated unsuccessfully with gonadotrophins and in-vitro fertilization. All three patients became ovulatory within the first month after UO. Two patients conceived 11 and 12 months after surgery respectively and delivered healthy babies. Testosterone concentrations decreased in two patients to upper values of the normal range and remained unchanged in one patient. We conclude that restoration of ovulation can be a beneficial side-effect of UO in clomiphene citrate resistant patients with PCOS and long-standing infertility.