A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

Problems in the treatment of malabsorption in CF

ABSTRACT. Several factors play a role in the cause of malabsorption in CF. Besides the enzyme deficiency in the secretion of the exocrine pancreas, decreased bile‐salt concentration in the gut may also be an important factor in the fat malabsorption. The contribution to the fat absorption by other lipases, such as lingual lipase and gastric lipase, remains to he proved. The therapeutic measures are only partly effective because of the breakdown of swalled enzymes by gastric acid. Some improvement is reached by using a new acid‐resistant coating for the enzyme supplement. Newly developed and essential for its success is the application of small coated particles to prevent retention in the stomach, and the easy breakdown of the coating in an alkaline solution. The treatment of the bile salt deficiency has not been successful until now. A trial with additional Tween 80, with the option of supplementing the detergent activity which was found to he successful in Crohn disease, was without marked success. Copyrigh

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Arabidopsis heterotrimeric G-protein regulates cell wall defense and resistance to necrotrophic fungi

The Arabidopsis heterotrimeric G-protein controls defense responses to necrotrophic and vascular fungi. The agb1 mutant impaired in the Gβ subunit displays enhanced susceptibility to these pathogens. Gβ/AGB1 forms an obligate dimer with either one of the Arabidopsis Gγ subunits (γ1/AGG1 and γ2/AGG2). Accordingly, we now demonstrate that the agg1 agg2 double mutant is as susceptible as agb1 plants to the necrotrophic fungus Plectosphaerella cucumerina. To elucidate the molecular basis of heterotrimeric G-protein-mediated resistance, we performed a comparative transcriptomic analysis of agb1-1 mutant and wild-type plants upon inoculation with P. cucumerina. This analysis, together with metabolomic studies, demonstrated that G-protein-mediated resistance was independent of defensive pathways required for resistance to necrotrophic fungi, such as the salicylic acid, jasmonic acid, ethylene, abscisic acid, and tryptophan-derived metabolites signaling, as these pathways were not impaired in agb1 and agg1 agg2 mutants. Notably, many mis-regulated genes in agb1 plants were related with cell wall functions, which was also the case in agg1 agg2 mutant. Biochemical analyses and Fourier Transform InfraRed (FTIR) spectroscopy of cell walls from G-protein mutants revealed that the xylose content was lower in agb1 and agg1 agg2 mutants than in wild-type plants, and that mutant walls had similar FTIR spectratypes, which differed from that of wild-type plants. The data presented here suggest a canonical functionality of the Gβ and Gγ1/γ2 subunits in the control of Arabidopsis immune responses and the regulation of cell wall composition

Zum biochemischen Wirkungsmechanismus des adrenocorticotropen Hormons

Es wird eine Übersicht über zwei Hypothesen und die dazugehörigen Befunde zum Wirkungsmechanismus des adrenocorticotropen Hormons gegeben: 1. Der Gehalt der Nebenniere an cyclischem Adenosinmonophosphat wird durch ACTH erhöht, die stimulierende Wirkung des Hormons auf die Corticoidsynthese wird durch cyclisches Adenosinmonophosphat imitiert. Die Beschleunigung der Corticoidsynthese dürfte allerdings nicht durch eine Aktivierung der Phosphorylase in der Nebenniere erfolgen. 2. Befunde zum biochemischen Mechanismus der Stimulation der Proteinsynthese in der Nebenniere durch ACTH werden referiert. Die Intaktheit der Proteinsynthese der Nebenniere scheint für den steroidogenen Effekt des ACTH Voraussetzung zu sein.Two current hypotheses on the mechanism of action of ACTH are reviewed: 1. The content of cyclic 3,5-adenosine monophosphate of the adrenals is increased by ACTH, and cyclic AMP or ACTH enhance corticoid synthesis. However, stimulation of corticoid synthesis presumably is not mediated by activation of adrenal phosphorylase. 2. Experiments dealing with the biochemical mechanism of the stimulation of adrenal protein synthesis are reviewed. The integrity of the adrenal protein synthesis appears to be necessary for the enhancement of corticoid synthesis by ACTH

Late gastrointestinal tissue effects after hypofractionated radiation therapy of the pancreas

Background To consolidate literature reports of serious late gastrointestinal toxicities after hypofractionated radiation treatment of pancreatic cancer and attempt to derive normal tissue complication probability (NTCP) parameters using the Lyman-Kutcher-Burman model. Methods Published reports of late grade 3 or greater gastrointestinal toxicity after hypofractionated treatment of pancreatic cancer were reviewed. The biologically equivalent dose in 1.8 Gy fractions was calculated using the EQD model. NTCP parameters were calculated using the LKB model assuming 1–5 % of the normal tissue volume was exposed to the prescription dose with α/β ratios of 3 or 4. Results A total of 16 human studies were examined encompassing a total of 1160 patients. Toxicities consisted of ulcers, hemorrhages, obstructions, strictures, and perforations. Non-hemorrhagic and non-perforated ulcers occurred at a rate of 9.1 % and were the most commonly reported toxicity. Derived NTCP parameter ranges were as follows: n = 0.38–0.63, m = 0.48–0.49, and TD50 = 35–95 Gy. Regression analysis showed that among various study characteristics, dose was the only significant predictor of toxicity. Conclusions Published gastrointestinal toxicity reports after hypofractionated radiotherapy for pancreatic cancer were compiled. Median dose was predictive of late grade ≥ 3 gastrointestinal toxicity. Preliminary NTCP parameters were derived for multiple volume constraints