Severity of acute hepatitis and its outcome in patients with dengue fever in a tertiary care hospital Karachi,Pakistan (South Asia)

Background  

Liver injury due to dengue viral infection is not uncommon. Acute liver injury is a severe complicating factor in dengue, predisposing to life-threatening hemorrhage, Disseminated Intravascular Coagulation (DIC) and encephalopathy. Therefore we sought to determine the frequency of hepatitis in dengue infection and to compare the outcome (length of stay, in hospital mortality, complications) between patients of Dengue who have mild/moderate (ALT 23-300 IU/L) v/s severe acute hepatitis (ALT > 300 IU/L).     

Marked response to single agent trastuzumab in a patient with metastatic HER-2 gene amplified rectal cancer

Overexpression or HER-2 gene amplification occurs in approximately 25% of invasive breast cancers and predicts response to the targeting therapeutic antibody trastuzumab (1). In this report, trastuzumab was used in the treatment of a patient with metastatic colorectal cancer harboring HER-2 gene amplification and overexpression. There was a marked radiographic response to the trastuzumab. If a larger series confirms the efficacy of trastuzumab use in patients with colorectal cancers with HER-2 gene amplification, trastuzumab could help improve the outlook for patients with this unusual colorectal cancer variant.     

Effect of expression of adenine phosphoribosyltransferase on the in vivo anti-tumor activity of prodrugs activated by E. coli purine nucleoside phosphorylase

The use of E. coli purine nucleoside phosphorylase (PNP) to activate prodrugs has demonstrated excellent activity in the treatment of various human tumor xenografts in mice. E. coli PNP cleaves purine nucleoside analogs to generate toxic adenine analogs, which are activated by adenine phosphoribosyl transferase (APRT) to metabolites that inhibit RNA and protein synthesis. We created tumor cell lines that encode both E. coli PNP and excess levels of human APRT, and have used these new cell models to test the hypothesis that treatment of otherwise refractory human tumors could be enhanced by overexpression of APRT. In vivo studies with 6-methylpurine-2'-deoxyriboside (MeP-dR), 2-F-2'-deoxyadenosine (F-dAdo) or 9-β-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate (F-araAMP) indicated that increased APRT in human tumor cells coexpressing E. coli PNP did not enhance either the activation or the anti-tumor activity of any of the three prodrugs. Interestingly, expression of excess APRT in bystander cells improved the activity of MeP-dR, but diminished the activity of F-araAMP. In vitro studies indicated that increasing the expression of APRT in the cells did not significantly increase the activation of MeP. These results provide insight into the mechanism of bystander killing of the E. coli PNP strategy, and suggest ways to enhance the approach that are independent of APRT.     

Cytopathological and chemico‐physical analyses of smears of mucosa surrounding oral piercing

Oral Diseases (2010) 16 , 160–166 Objective: The aim of this comparative study was to analyze cytopathologically and chemico‐physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. Materials and methods: The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back‐scattered) scanning electron microscope (SEM) and X‐ray microanalysis to study piercing fragments. Results: Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X‐ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. Conclusions: The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.     

Olfaction in dentistry

Oral Diseases (2010) 16 , 221–232 Practitioners of oral medicine frequently encounter patients with complaints of taste disturbance. While some such complaints represent pathological processes specific to the gustatory system, per se, this is rarely the case. Unless taste‐bud mediated qualities such as sweet, sour, bitter, salty, umami, chalky, or metallic are involved, ‘taste’ dysfunction inevitably reflects damage to the sense of smell. Such ‘taste’ sensations as chicken, chocolate, coffee, raspberry, steak sauce, pizza, and hamburger are dependent upon stimulation of the olfactory receptors via the nasopharynx during deglutition. In this paper, we briefly review the anatomy, physiology, and pathophysiology of the olfactory system, along with means for clinically assessing its function. The prevalence, etiology, and nature of olfactory disorders commonly encountered in the dental clinic are addressed, along with approaches to therapy and patient management.     

A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation

Background

β-Amyloid precursor protein (APP) has been reported to play a role in the outgrowth of neurites from cultured neurons. Both cell-surface APP and its soluble, ectodomain cleavage product (APPs-α) have been implicated in regulating the length and branching of neurites in a variety of assays, but the mechanism by which APP performs this function is not understood.

Results

Here, we report that APP is required for proper neurite outgrowth in a cell autonomous manner, both in vitro and in vivo. Neurons that lack APP undergo elongation of their longest neurite. Deletion of APLP1 or APLP2, homologues of APP, likewise stimulates neurite lengthening. Intriguingly, wild-type neurons exposed to APPs-α, the principal cleavage product of APP, also undergo neurite elongation. However, APPs-α is unable to stimulate neurite elongation in the absence of cellular APP expression. The outgrowth-enhancing effects of both APPs-α and the deletion of APP are inhibited by blocking antibodies to Integrin β1 (Itgβ1). Moreover, full length APP interacts biochemically with Itgβ1, and APPs-α can interfere with this binding.

Conclusion

Our findings indicate that APPs-α regulates the function of APP in neurite outgrowth via the novel mechanism of competing with the binding of APP to Itgβ1.