In situ detection of hepatitis C virus RNA in salivary glands

Chronic hepatitis C virus (HCV) infection has been associated with several extrahepatic manifestations, among these, to diseases with oral manifestations such as Sj?gren's syndrome or sialadenitis. HCV-RNA has been detected in saliva and in salivary glands from patients with sialadenitis by polymerase chain reaction. However, morphological evidence of HCV replication in salivary gland cells is needed to support a role for HCV in causing sialadenitis or Sj?gren's syndrome. We have used in situ hybridization and immunohistochemistry to analyze the presence of HCV-RNA of sense and antisense polarity and HCV core antigen, respectively, in salivary gland biopsies from 19 patients with chronic sialadenitis or Sj?gren's syndrome (eight anti-HCV-positive; 11 anti-HCV-negative). HCV-RNA of both positive and negative polarity as well as HCV core antigen were detected in the epithelial cells of the salivary gland biopsies from all of the anti-HCV-positive patients but in none of the anti-HCV-negative cases. The percentage of HCV-infected cells ranged from 25 to 48.8% in the patients studied. In conclusion, we have shown that HCV infects and replicates in the epithelial cells from salivary glands of patients with Sj?gren's syndrome or chronic sialadenitis. However, its implication in the pathogenesis of these diseases deserves future research.     

Effect of cervical spinal cord stimulation on regional blood flow and oxygenation in advanced head and neck tumours.

BACKGROUND: Tumour ischaemia leads to decreased delivery of oxygen, chemotherapy and radiosensitisers. Hypoxia in head and neck (H&N) tumours is an important adverse prognostic factor. Spinal cord stimulation (SCS) is a well-established neurosurgical technique in the treatment of several ischaemic syndromes. This prospective study evaluated the effect of cervical-SCS on common carotid artery (CCA) blood flow and tumour oxygenation in patients with advanced H&N cancer. PATIENTS AND METHODS: Sixteen patients with advanced H&N tumours were enrolled. Cervical-SCS devices were inserted subcutaneously prior to commencement of scheduled chemoradiotherapy. Pre- and post-SCS measurements were as follows: (i) tumour oxygenation (mmHg) using polarographic probes; (ii) blood flow quantification (ml/min) and diastolic and systolic velocimetry (cm/s) in the CCA using colour Doppler. RESULTS: After SCS, median tumour oxygenation increased in two-thirds of patients (34%; P = 0.023), all patients had improved CCA blood flow (50%; P <0.001) and almost all patients showed an increased CCA diastolic velocity (26%; P = 0.003) and systolic velocity (20%; P = 0.011). CONCLUSIONS: Cervical-SCS increased tumour oxygenation and CCA blood flow, and could enhance the loco-regional delivery of oxygen, radiosensitising and chemotherapeutic drugs. Cervical-SCS as adjuvant in chemoradiotherapy of these tumours warrants further investigation.     

Nephrotic Syndrome: Components,Connections, and Angiopoietin-Like 4–Related Therapeutics

Nephrotic syndrome is recognized by the presence of proteinuria in excess of 3.5 g/24 h along with hypoalbuminemia, edema, hyperlipidemia (hypertriglyceridemia and hypercholesterolemia), and lipiduria. Each component has been investigated individually over the past four decades with some success. Studies published recently have started unraveling the molecular basis of proteinuria and its relationship with other components. We now have improved understanding of the threshold for nephrotic-range proteinuria and the pathogenesis of hypertriglyceridemia. These studies reveal that modifying sialylation of the soluble glycoprotein angiopoietin-like 4 or changing key amino acids in its sequence can be used successfully to treat proteinuria. Treatment strategies on the basis of fundamental relationships among different components of nephrotic syndrome use naturally occurring pathways and have great potential for future development into clinically relevant therapeutic agents.     

Prevention of haloperidol-induced alterations in brain acetylcholinesterase activity by vitamins B co-administration in a rodent model of tardive dyskinesia

Tardive dyskinesia (TD) is an iatrogenic syndrome being a significant adverse outcome of typical and atypical antipsychotic therapy. Recently we demonstrated that vitamins B (B1, B6, B12 alone or in combination) were able to prevent haloperidol-induced orofacial dyskinesia (OD) possibly by their antioxidant activity in the striatum, using a well-established model of TD. Here, based on the fact that alterations in cholinergic neurotransmission are related to TD pathophysiology and that vitamins B seems to influence brain cholinergic neurotransmission, we decided to investigate the effects of vitamins B1, B6, B12 and their association, vitamin B cocktail in haloperidol-induced cholinergic alterations, evaluated by alterations in acetylcholinesterase (AChE) activity, in striatum, prefrontal cortex and hippocampus, as a way to determine the participation of cholinergic neurotransmission, in these vitamins antidyskinetic mechanism. Haloperidol 1 mg/kg?i.p. daily administration during 21 days to Wistar rats caused OD while decreased AChE activity in all brain areas studied. Vitamins B administration (B1:B6:B12 at 60:60:0.6 mg/kg, s.c) alone and vitamin B cocktail co-administered with haloperidol prevented OD development and increased AChE activity in all brain areas studied, with the maximum activity increment observed in the hippocampus of the animals co-treated with vitamin B12 and vitamin B cocktail. The antidyskinetic drug, clozapine did not induce OD and increased AChE activity similarly to the groups coadministered with vitamin B and HAL. The present data suggest that vitamins B can prevent haloperidol-induced alterations in AChE activity what can be related to the mechanism underlying their antidyskinetic effect.     

Immunocytochemical detection in eel corpuscles of stannius of a mammalian parathyroid-like hormone

Stannius corpuscles of the eel synthesize and secrete a mammalian parathyroid-like hormone called parathyrin of CS (PCS). PCS has been localized in the cytoplasm of all cells in the corpuscles, detection being by indirect immunofluorescence with an antiserum anti-1–84 bovine hormone (PTH). The specificity of the reaction was demonstrated by inhibition of the fluorescent staining with 1–84 bovine PTH and the active fragment 1–34 of human PTH. Variations of the cellular localization of the PCS or a complete depletion of the hormonal content, in all cells, were observed in eels made hypercalcemic by Ca overloading. The secretory activity of the two types of CS cells may be regulated by the plasma Ca²⁺ concentration.