Modification of physicochemical properties of chitosan to improve its pharmaceutical and agrochemical potential applications.

Chitosan has received much more attention as a functional biopolymer with applications in pharmaceuticals, agricultural, drug delivery systems and cosmetics. The objectives of present investigation were to carry out modification of chitosan for enhancement of aqueous solubility, which will impart increased solubility and dissolution rate of poorly soluble drug itraconazole (ITZ) and also evaluate the modified chitosan for soyabean seed germination studies. The modification of chitosan was accomplished through the antisolvent precipitation method; employing five carboxylic acids. The resulting products were assessed for changes in molecular weight, degree of deacetylation, solubility and solid state characterization. Subsequently, the modified chitosan was complexed with itraconazole using the co-grinding technique. The prepared formulations were evaluated for solubility, FTIR (Fourier-transform infrared spectroscopy), PXRD (Powder X-ray diffraction), in-vitro dissolution studies. Furthermore the effect of modified chitosan has been evaluated on soybean seed germination. Results demonstrated that, modified chitosan improves self and solubility of itraconazole by six folds. As there was increased degree of deacetylation of chitosan leads to improvement in solubility. The results of FTIR showed the slight shifting of peaks in co-grind formulations of itraconazole. Formulations showed reduction in crystallinity of drug which leads to enhancement in dissolution rate as compared to pure itraconazole. Retention of property of seed germination was observed with modified chitosan at optimum concentration of 3 % w/v, with benefit of enhanced aqueous solubility of chitosan. This positive result paves the way for the advancement of pharmaceutical and agrochemical products employing derivatives of chitosan.

Concomitant pulmonary disease is common among patients with extrapulmonary TB.

BACKGROUND: Microbiologic screening of extrapulmonary TB (EPTB) patients could inform recommendations for aerosol precautions and close contact prophylaxis. However, this is currently not routinely recommended in India. Therefore, we estimated the proportion of Indian patients with EPTB with microbiologic evidence of pulmonary TB (PTB).METHODS: We characterized baseline clinical, radiological and sputum microbiologic data of 885 adult and pediatric TB patients in Chennai and Pune, India, between March 2014 and November 2018.RESULTS: Of 277 patients with EPTB, enhanced screening led to the identification of 124 (45%) with concomitant PTB, including 53 (19%) who reported a cough >2 weeks; 158 (63%) had an abnormal CXR and 51 (19%) had a positive sputum for TB. Of 70 participants with a normal CXR and without any cough, 14 (20%) had a positive sputum for TB. Overall, the incremental yield of enhanced screening of patients with EPTB to identify concomitant PTB disease was 14% (95% CI 12-16).CONCLUSIONS: A high proportion of patients classified as EPTB in India have concomitant PTB. Our results support the need for improved symptom and CXR screening, and recommends routine sputum TB microbiology screening of all Indian patients with EPTB.

Role of heterotrophic nitrifiers and aerobic denitrifiers in simultaneous nitrification and denitrification process: a nonconventional nitrogen removal pathway in wastewater treatment.

Bacterial species capable of performing both nitrification and denitrification in a single vessel under similar conditions have gained significance in the wastewater treatment scenario considering their unique character of performing the above reactions under heterotrophic and aerobic conditions respectively. Such a novel strategy often referred to as simultaneous nitrification and denitrification (SND) has a tremendous potential in dealing with various wastewaters having low C : N content, considering that the process needs very little or no external carbon source and oxygen supply thus adding to its cost-effective and environmentally friendly nature. Though like other micro-organisms, heterotrophic nitrifiers and aerobic denitrifiers convert inorganic or organic nitrogen-containing substances into harmless dinitrogen gas in the wastewater, their ecophysiological role in the global nitrogen cycle is still not fully understood. Attempts to highlight the role played by the heterotrophic nitrifiers and aerobic denitrifiers in dealing with nitrogen pollution under various environmental operating conditions will help in developing a mechanistic understanding of the SND process to address the issues faced by the traditional methods of aerobic autotrophic nitrification-anaerobic heterotrophic denitrification.

Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes.

INTRODUCTION: Testing for anti-TB drugs in small hair samples may serve as a non-invasive tool to measure cumulative drug exposure and/or adherence, as these determine treatment success. We aimed to assess how well hair assays of TB drugs predict TB treatment outcomes.METHODS: A small thatch of hair, ~30 strands, was cut from the occipital region in adults and children from a prospective TB cohort in India. Isoniazid (INH), acetyl-INH and pyrazinamide (PZA) were extracted from the hair samples and quantified using liquid-chromatography-tandem mass spectrometry. The relationship between drug concentrations in hair and time to unfavourable outcomes was assessed using Cox-proportional hazards regression models.RESULTS: A two-fold increase in hair acetyl-INH concentrations in the 264 participants in our cohort with hair assays for TB drugs indicated a lower hazard of unfavourable TB treatment outcomes (aHR 0.67, 95%CI 0.44-1.02) and TB treatment failure (aHR 0.65, 95%CI 0.42-1.01). Higher summed concentrations (a summed measure of INH and acetyl-INH) indicated a lower hazard of treatment failure (aHR 0.69, 95%CI 0.45-1.05)CONCLUSION: Hair levels of INH and its metabolite may predict TB treatment outcomes, indicating the potential utility of this measure to assess and optimise TB treatment outcomes.

Assessment of the Xpert assay among adult pulmonary tuberculosis suspects with and without diabetes mellitus.

SETTING: Pune and Pimpri-Chinchwad Municipal Corporation area, Maharashtra State, India.OBJECTIVE: To assess the sensitivity and specificity of the Xpert® MTB/RIF assay among adults with suspected pulmonary tuberculosis (PTB) and with or without diabetes (DM).DESIGN: As part of a prospective cohort study, we screened 2359 adults presumed to have PTB with no history of TB. All individuals underwent testing for two sputum smears, culture, Xpert, glycated haemoglobin and fasting blood sugar. We calculated sensitivity and specificity of Xpert by comparing it with TB sputum culture result as a gold standard.RESULTS: Among screened individuals, 483 (20%) were diagnosed with DM and 1153 (49%) with pre-DM; 723 (31%) had no DM. Overall sensitivity of Xpert was 96% (95%CI 95-97) and specificity was 91% (95%CI 89-93). Xpert sensitivity was significantly higher among DM group (98%) than in the 'No DM' (95%; P < 0.01) and pre-DM (96%; P < 0.05) groups. Among sputum smear-negative individuals, Xpert sensitivity was higher in the DM group than in the No DM (92% vs. 82%; P = 0.054) and pre-DM group (92% vs. 82%; P = 0.037).CONCLUSION: High sensitivity and specificity of Xpert underscores the need for its rapid scale up for the early detection of TB in settings with a high dual burden of TB and DM.

[Endovascular aneurysm repair (EVAR) : Complication management]. / Endovaskuläre Aneurysmaversorgung (EVAR) : Komplikationsmanagement.

A variety of complications may be experienced during or after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA). Acute procedure-related complications include injury to the access vessels, improper endograft placement, ischaemic and systemic complications as well as the postimplantation syndrome. Femoral pseudoaneurysms, endograft migration, kinking or occlusion, endoleaks and endograft infection are complications that have been observed at follow-up. Meticulous patient selection and preprocedural work-up can reduce the incidence of these complications. The majority of the complications, acute as well those at follow-up, can be dealt with endoluminally. It is of essence, however, that a wide variety of catheters, guidewires, stents, stent-grafts and embolics are readily available in the repertoire of the interventionalist. In a small number of patients with endograft occlusion or infection or with bleeding complications/pseudoaneurysms of the access vessels, open surgical intervention may become necessary. To obtain optimal results, close interdisciplinary co-operation, especially between the interventionist, the vascular surgeon and the anaesthetist is mandatory.

Comparative Evaluation of N-Butyl Cyanoacrylate and Silk Sutures on Healing of Periodontal Flaps: A Clinico Histological Evaluation.

Background The periodontal flap is one of the most frequently employed procedures. Closure of reflected flap is important step in flap surgery. Black silk sutures are most often used material in routine surgical procedures. These suture materials demand more time and effort and expertise from the surgeon. Tissue adhesives have been developed as alternatives to overcome these problems such as cyanoacrylates. Objective The present study is an attempt to compare effectiveness of the black silk suture with cyanoacrylate adhesives in closing reflected periodontal flap. Method Thirty systemically healthy patients who underwent bilateral flap surgery were given 3-0 black silk sutures on one side and N-butyl cyanoacrylate adhesive on the other side to close a surgical incision. All the participants in the study were recalled on the seventh, 21st, 42nd day. Participants were evaluated for healing and plaque accumulation by assessing the gingival index, plaque index, wound healing index. Biopsy specimens were obtained on seventh and 42nd postoperative day. Result The amount of inflammation was less during the first week of healing when cyanoacrylate was compared with silk. However, over a period of 21 days to 42 days, the sites treated with both the materials showed similar healing patterns without any significant difference in the evaluated parameter. Conclusion The result of the study showed that the use of cyanoacrylate for the closure of periodontal flaps results in better initial post-operative healing as compared to closure with silk suture and that this method of closure can be advocated in a routine surgical periodontal practice.

Pumping liquid metal at high temperatures up to 1,673 kelvin.

Heat is fundamental to power generation and many industrial processes, and is most useful at high temperatures because it can be converted more efficiently to other types of energy. However, efficient transportation, storage and conversion of heat at extreme temperatures (more than about 1,300 kelvin) is impractical for many applications. Liquid metals can be very effective media for transferring heat at high temperatures, but liquid-metal pumping has been limited by the corrosion of metal infrastructures. Here we demonstrate a ceramic, mechanical pump that can be used to continuously circulate liquid tin at temperatures of around 1,473-1,673 kelvin. Our approach to liquid-metal pumping is enabled by the use of ceramics for the mechanical and sealing components, but owing to the brittle nature of ceramics their use requires careful engineering. Our set-up enables effective heat transfer using a liquid at previously unattainable temperatures, and could be used for thermal storage and transport, electric power production, and chemical or materials processing.

Risk of cancer incidence before the age of 15 years after exposure to ionising radiation from computed tomography: results from a German cohort study.

The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54-2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.

[The simultaneous appearance of three uncommon tumours]. / Synchrones Auftreten dreier seltener Tumoren.

A 70-year-old woman presented with nasal obstruction and pain projecting onto the left cheek. The face seemed asymmetric including exophthalmus on the right side. Nasal endoscopic inspection revealed a sarcomatous tumor located on the middle turbinate. The CT showed that the tumor filled the left maxillary sinus completely and had eroded the maxillary bone. In addition, a round, sharply defined intraorbital neoplasm on the right side was identified in the contrast-enhanced MRI. Histological examination of the extirpated intraorbital tumour showed a neurilemmoma. A tissue biopsy of the intranasal tumour falsely suggested an intestinal adenocarcinoma. Multiple neoplasms suspicious of disseminated lung metastases were detected in the CT of the thorax. One round lesion removed by thoracoscopy revealed a carcinoid. The intranasal tumour was excised completely and the histology proved beyond doubt an inverted papilloma.

Dictyostelium, a microbial model for brain disease.

BACKGROUND: Most neurodegenerative diseases are associated with mitochondrial dysfunction. In humans, mutations in mitochondrial genes result in a range of phenotypic outcomes which do not correlate well with the underlying genetic cause. Other neurodegenerative diseases are caused by mutations that affect the function and trafficking of lysosomes, endosomes and autophagosomes. Many of the complexities of these human diseases can be avoided by studying them in the simple eukaryotic model Dictyostelium discoideum. SCOPE OF REVIEW: This review describes research using Dictyostelium to study cytopathological pathways underlying a variety of neurodegenerative diseases including mitochondrial, lysosomal and vesicle trafficking disorders. MAJOR CONCLUSIONS: Generalised mitochondrial respiratory deficiencies in Dictyostelium produce a consistent pattern of defective phenotypes that are caused by chronic activation of a cellular energy sensor AMPK (AMP-activated protein kinase) and not ATP deficiency per se. Surprisingly, when individual subunits of Complex I are knocked out, both AMPK-dependent and AMPK-independent, subunit-specific phenotypes are observed. Many nonmitochondrial proteins associated with neurological disorders have homologues in Dictyostelium and are associated with the function and trafficking of lysosomes and endosomes. Conversely, some genes associated with neurodegenerative disorders do not have homologues in Dictyostelium and this provides a unique avenue for studying these mutated proteins in the absence of endogeneous protein. GENERAL SIGNIFICANCE: Using the Dictyostelium model we have gained insights into the sublethal cytopathological pathways whose dysregulation contributes to phenotypic outcomes in neurodegenerative disease. This work is beginning to distinguish correlation, cause and effect in the complex network of cross talk between the various organelles involved. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

Synthesis and pharmacological evaluation of antiinflammatory mutual amide prodrugs.

Nonsteroidal antiinflammatory drugs have been widely used for the management of inflammation, pain and nociception. Gastric intolerance caused by most of the nonsteroidal antiinflammatory drugs used today restricts their use. Several approaches have been proposed to modify the parent nonsteroidal antiinflammatory drugs molecule in order to reduce their gastric toxicity. Oral prodrug approach is one of such approaches. In the present work three nonsteroidal antiinflammatory drugs viz. ibuprofen, diclofenac, and flurbiprofen were conjugated with sulfonamides like sulphamethoxazole and sulphanilamide via amide bond using dicyclohexylcarbodiimide coupling reaction. The synthesized prodrugs were screened for their analgesic and antiinflammatory activity using Eddy's hot plate, acetic acid-induced writhing and carrageenan-induced rat paw edema method, respectively. These prodrugs were also evaluated for their ulcerogenic potential. All synthesized prodrugs were found to be less ulcerogenic than their parent nonsteroidal antiinflammatory drugs and showed better activity profile in terms of analgesic and antiinflammatory activity as compared to their respective parent drugs.

HDAC inhibitors - new generation of target specific treatment.

Histone Deacetylases (HDACs) enzymes are critical in regulating gene expression and transcription. They also play a fundamental role in regulating cellular activities such as cell proliferation, survival and differentiation. Inhibition of HDACs has generated many fascinating results including a new strategy in human cancer therapy. HDAC Inhibitors (HDACIs) like SAHA, TSA are emerging as new promising drugs for various anti-inflammatory and CNS-disorders. This review, along with chemical classification, emphasizes on the therapeutic potential of various HDACIs against different diseases.

[Peripheral vascular disease of iliac and femoro-popliteal arteries: state-of-the-art endoluminal revascularization]. / Arterielle Verschlusskrankheit der Becken- und Oberschenkelarterien: State-of-the-art-Rekanalisation.

Endoluminal therapy is indicated in lower extremity ischaemia with Fontaine grades IIb, III and IV. In the presence of significant limitations, interventions are carried out even in grade IIa claudicants. In addition to the TASC A and B lesions, TASC C and D lesions are increasingly being treated endoluminally as well. Presently, technical success rates of revascularization procedures are above 90% in the iliac vessels and between 79% and 95% in the femoro-popliteal segments. Concentric, non-calcified iliac stenoses are primarily treated with balloon angioplasty (PTA) followed by optional stenting when necessary. For occlusions and heavily calcified lesions, primary stenting is recommended. Primary PTA is the mainstay of treatment in femoro-popliteal vessels with stents being used as a "bail-out" option in case of suboptimal PTA. However, initial reports proving the superiority of primary stenting over PTA with optional stenting have already appeared. Results of PTA with drug-coated balloons for prevention of early restenosis are promising. In the near future, primary PTA with optional stenting in the femoro-popliteal segments may give way to drug-coated balloon angioplasty or primary stenting.

[Stent-graft implantation in the thoracic aorta. Results of an interdisciplinary survey in Germany]. / Thorakale Aorten-Stentgraftimplantation. Ergebnisse einer interdisziplinären Umfrage in Deutschland.

BACKGROUND AND OBJECTIVE: Endovascular stent-graft placement is emerging as a novel therapeutic option in patients with disease of the descending thoracic aorta. Quality standards for performing stent-graft procedures as well as for pre- and postoperative patient management are lacking, so far. It was the aim of this present survey to assess the current therapeutic standard of thoracic aortic stent-graft placement in Germany. METHODS: In a nationwide survey, a total of 206 vascular surgical, radiologic, cardiologic, and cardiothoracic surgical departments were contacted. Data concerning preoperative procedure planning, logistics, practical/technical issues of stent-graft placement, and postoperative patient management were evaluated using a standardized questionnaire comprising 29 items. Data analysis was performed using univariate analysis. RESULTS: 184 (89.3 %) of the 206 departments participated in the survey. Of these, 71 centers reported intending to perform or having performed thoracic aortic stent-graft placement. The survey overall represents 2267 endovascular stent-graft procedures performed in Germany between 1997/98 and 2003. On average, 7.4 stent-graft procedures/year were performed by each center, with half the centers performing fewer than 5 procedures/year. Thoracic aortic aneurysms was the main indication for endovascular stent-graft placement, followed by aortic dissection. There were significant differences between the different medical specialties which perform stent-graft procedures with respect to indications, choice of preoperative and intraoperative imaging methods, and technical equipment. There was strong agreement between the different centers concerning the necessity of a life-long follow-up after stent-graft placement, with computed tomography being the preferred imaging technique (90 % of centers). CONCLUSION: The present survey documents an increasing use of endovascular stent-graft placement in patients with disease of the descending thoracic aorta. There were differences regarding the technical execution of this procedures between specialties with respect to indication, procedure planning, and practical-technical aspects of stent-graft placement.

Chemoocclusion vs chemoperfusion for treatment of advanced hepatocellular carcinoma: a randomised trial.

AIMS: Transarterial chemoembolization (TACE) can be associated with considerable toxicity and treatment-associated mortality. Transient transarterial chemoocclusion (TACO) using degradable starch microspheres (DSM) has been proposed as a potentially safer alternative while maintaining anti-tumour efficiency. In a randomised phase II trial TACO was compared to transarterial chemoperfusion without DSM (TACP). METHODS: Seventy-four patients with advanced HCC were randomised to two treatment arms: (i) TACO (600-1200 mg DSM) and (ii) TACP. In both arms regional chemotherapy consisted of cisplatin (100 mg/m2) and doxorubicin (60 mg/m2). Both arms were corresponding in terms of age, gender, liver performance state, and tumour-stage. A maximum of six treatment cycles was applied in monthly intervals. Follow-up was performed in terms of tumour response, time to progression, survival and quality of life. RESULTS: Tumour response rates did not differ significantly between the two treatment arms, however, there was a tendency towards higher response rates in the TACO arm (TACO vs TACP): partial response: 26 vs 9%, stable disease: 41 vs 55%, progressive disease: 33 vs 36%. Time to tumour progression (32 vs 27 weeks), and overall survival (60 vs 69 weeks) were not significantly different. Grade 4 adverse events were rare in both arms and treatment-associated mortality was not observed. In addition, there was no significant difference in terms of quality of life under therapy (EORTC). CONCLUSION: TACO with DSM did not improve response or survival significantly compared to TACP in advanced non-resectable HCC.

Yersinia infection mimicking recurrence of gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. So far, surgical resection has been the only curative treatment, but new options became available with the application of imatinib (Glivec) as a specific molecular inhibitor. Even after complete resection, GISTs have a high rate of recurrence and disease-linked mortality. Here we report on the case of a clinically well 57-year-old woman who presented to us 3 years after resection of a GIST of the small intestine. Abdominal ultrasound and CT scan showed intestinal wall thickening in the area of anastomosis and mesenteric lymphadenopathy, suggesting a recurrence of the primary GIST. However, serological testing was positive for yersinia antibodies. Surgical exploration revealed an asymptomatic infection with Yersinia enterocolitica serotype O9, proven by positive culture and histology, which showed no evidence of malignancy. Prognostic variables for GIST as well as diagnostic measures and limitations for yersiniosis are discussed. In the end, only surgical exploration and histological analysis could establish the final diagnosis. In conclusion, GISTs have a high likelihood of recurrence even after complete resection, but an asymptomatic infection such as yersiniosis must be considered as a differential diagnosis to GIST recurrence.