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Corporate social responsibility (CSR) is a progressively significant issue for organizations and governments. To benefit from a good reputation that reflects on organizational performance, organizations must ensure the balance between stakeholders' needs. This paper studies the direct and indirect effects of CSR on organizational financial performance as perceived by employees of organizations. The investigation used structural equation modeling to evaluate and describe the nature of the relationship between these two variables. The empirical study uses a perceptual approach, evaluating the perceptions of the closest stakeholders (employees). Data on the perceptions of 431 employees in Romanian organizations were collected following a questionnaire-based survey. The results indicate a strong effect of social responsibility on both direct and mediated organizational financial performance. The relationships established with the stakeholders ultimately affect organizational financial performance through variables such as the attraction and retention of employees, the attraction and loyalty of customers, more accessible access to capital, and the organization's reputation.

Social responsibility (SR) is a concept or practice by which organizations take into account the interest of society by taking responsibility for the impact of their activities on all stakeholders. The SR of organizations implies ethical behavior concerning all stakeholders and a company's commitment to the sustainable economic development of society. Organizational ethics is a set of written and unwritten codes of principles and values that govern decisions and actions within an organization. Ethics has a rather internal perspective, while social responsibility has a rather external perspective. This study examines the impact of social responsibility and organizational ethics on employees' wellbeing. To perform the empirical analysis, we conducted a survey among 423 employees from Romanian organizations. Using the structural equation modeling, we analyzed the relationships between social responsibility, organizational ethics, and employees' wellbeing, emphasizing the positive impact of ethical and responsible behavior of the organization on the employees' wellbeing. The organization's employees play a dual role: firstly, they are all internal stakeholders, and secondly, they are constituents of an external stakeholder essential for the organization-the community. The results show a significant positive influence of social responsibility and organizational ethics on employees' wellbeing as a result of a responsible and ethical behavior in relation to the organizational stakeholders.

A major challenge in validating genetic causes for patients with rare diseases (RDs) is the difficulty in identifying other RD patients with overlapping phenotypes and variants in the same candidate gene. This process, known as matchmaking, requires robust data sharing solutions to be effective. In 2014 we launched PhenomeCentral, a RD data repository capable of collecting computer-readable genotypic and phenotypic data for the purposes of RD matchmaking. Over the past 7 years PhenomeCentral's features have been expanded and its data set has consistently grown. There are currently 1615 users registered on PhenomeCentral, which have contributed over 12,000 patient cases. Most of these cases contain detailed phenotypic terms, with a significant portion also providing genomic sequence data or other forms of clinical information. Matchmaking within PhenomeCentral, and with connections to other data repositories in the Matchmaker Exchange, have collectively resulted in over 60,000 matches, which have facilitated multiple gene discoveries. The collection of deep phenotypic and genotypic data has also positioned PhenomeCentral well to support next generation of matchmaking initiatives that utilize genome sequencing data, ensuring that PhenomeCentral will remain a useful tool in solving undiagnosed RD cases in the years to come., (© 2022 Wiley Periodicals LLC.)

Background: The endocytic reabsorption of proteins in the proximal tubule requires a complex machinery and defects can lead to tubular proteinuria. The precise mechanisms of endocytosis and processing of receptors and cargo are incompletely understood. EHD1 belongs to a family of proteins presumably involved in the scission of intracellular vesicles and in ciliogenesis. However, the relevance of EHD1 in human tissues, in particular in the kidney, was unknown., Methods: Genetic techniques were used in patients with tubular proteinuria and deafness to identify the disease-causing gene. Diagnostic and functional studies were performed in patients and disease models to investigate the pathophysiology., Results: We identified six individuals (5-33 years) with proteinuria and a high-frequency hearing deficit associated with the homozygous missense variant c.1192C>T (p.R398W) in EHD1 . Proteinuria (0.7-2.1 g/d) consisted predominantly of low molecular weight proteins, reflecting impaired renal proximal tubular endocytosis of filtered proteins. Ehd1 knockout and Ehd1 R398W/R398W knockin mice also showed a high-frequency hearing deficit and impaired receptor-mediated endocytosis in proximal tubules, and a zebrafish model showed impaired ability to reabsorb low molecular weight dextran. Interestingly, ciliogenesis appeared unaffected in patients and mouse models. In silico structural analysis predicted a destabilizing effect of the R398W variant and possible inference with nucleotide binding leading to impaired EHD1 oligomerization and membrane remodeling ability., Conclusions: A homozygous missense variant of EHD1 causes a previously unrecognized autosomal recessive disorder characterized by sensorineural deafness and tubular proteinuria. Recessive EHD1 variants should be considered in individuals with hearing impairment, especially if tubular proteinuria is noted., (Copyright © 2022 by the American Society of Nephrology.)

Enamel renal syndrome (ERS) is a rare autosomal recessive disorder not fully characterized. Here we investigated ERS characteristics in 11 patients from 5 Brazilian families through clinical examination, imaging, renal ultrasonography, laboratory tests and DNA sequencing. The patients' age ranged from 6 to 25 years-old, and the presence of hypoplastic amelogenesis imperfecta, microdontia, intra-pulpal calcification, impacted posterior teeth with hyperplastic pericoronal follicles, gingival fibromatosis, ectopic calcifications on gingival and pericoronal tissues, and nephrocalcinosis were common findings to all patients. Only 4 patients showed abnormal laboratory tests (vitamin D, parathyroid hormone, phosphate, calcium). Intellectual disability and renal cysts were present in 2 patients each. Biallelic loss of function mutation in FAM20A gene, characterized by one base pair deletion in exon 11, resulting in a frameshift replacing a glutamine at codon 483 for a lysine and terminating at position 24 [NG_029809.1: c.1447delG; p.(Glu483Lysfs*24)], was detected in all patients, strongly suggesting a founder effect. Our results reinforce the distinct orofacial features of ERS, which are the clue for kidney examination and genetic testing. Early diagnosis is essential to minimize the deleterious effects related to ERS. Here we report the largest series of patients with ERS in a same population, and describe, for the first time, a founder mutation for FAM20A., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure. Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations. Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death. Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis., (Copyright © 2018 by the American Society of Nephrology.)

Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognized genetic disorder. Whole-genome linkage analysis in five informative families identified a single significant locus on chromosome 16p13.2 (logarithm of odds score 6.5). Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, we found in all patients a promoter mutation (c.-167G>T) in the phosphomannomutase 2 gene ( PMM2 ), either homozygous or in trans with PMM2 coding mutations. PMM2 encodes a key enzyme in N-glycosylation. Abnormal glycosylation has been associated with PKD, and we found that deglycosylation in cultured pancreatic β cells altered insulin secretion. Recessive coding mutations in PMM2 cause congenital disorder of glycosylation type 1a (CDG1A), a devastating multisystem disorder with prominent neurologic involvement. Yet our patients did not exhibit the typical clinical or diagnostic features of CDG1A. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2 We propose that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. Our findings extend the spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 pleiotropy., (Copyright © 2017 by the American Society of Nephrology.)

Enamel-renal syndrome (OMIM #204690) is an uncommon disorder characterized by amelogenesis imperfecta and nephrocalcinosis and is caused by mutations in FAM20 A. We report 2 patients with enamel-renal syndrome who exhibited the typical features of this syndrome and a homozygous nonsense mutation in the FAM20 A gene (c.406 C>T), genetically confirming the diagnosis. They also exhibited 2 undescribed clinical features, hypertrichosis and hearing loss. Alterations in genes frequently associated with nonsyndromic hearing loss in the Brazilian population, including connexin 26 (GJB2), connexin 30 (GJB6) and mitochondrial 12 S rRNA (m.A1555 G mutation), were not found. These results suggest a putative function of FAM20 A in the development of the inner ear and in the formation of hair. The presence of nephrocalcinosis is a risk factor for renal impairment, and it is important to perform regular renal monitoring in order to avoid renal failure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The National Institutes of Health Undiagnosed Diseases Program (NIH UDP) applies translational research systematically to diagnose patients with undiagnosed diseases. The challenge is to implement an information system enabling scalable translational research. The authors hypothesized that similar complex problems are resolvable through process management and the distributed cognition of communities. The team, therefore, built the NIH UDP integrated collaboration system (UDPICS) to form virtual collaborative multidisciplinary research networks or communities. UDPICS supports these communities through integrated process management, ontology-based phenotyping, biospecimen management, cloud-based genomic analysis, and an electronic laboratory notebook. UDPICS provided a mechanism for efficient, transparent, and scalable translational research and thereby addressed many of the complex and diverse research and logistical problems of the NIH UDP. Full definition of the strengths and deficiencies of UDPICS will require formal qualitative and quantitative usability and process improvement measurement.

Despite the increasing prevalence of clinical sequencing, the difficulty of identifying additional affected families is a key obstacle to solving many rare diseases. There may only be a handful of similar patients worldwide, and their data may be stored in diverse clinical and research databases. Computational methods are necessary to enable finding similar patients across the growing number of patient repositories and registries. We present the Matchmaker Exchange Application Programming Interface (MME API), a protocol and data format for exchanging phenotype and genotype profiles to enable matchmaking among patient databases, facilitate the identification of additional cohorts, and increase the rate with which rare diseases can be researched and diagnosed. We designed the API to be straightforward and flexible in order to simplify its adoption on a large number of data types and workflows. We also provide a public test data set, curated from the literature, to facilitate implementation of the API and development of new matching algorithms. The initial version of the API has been successfully implemented by three members of the Matchmaker Exchange and was immediately able to reproduce previously identified matches and generate several new leads currently being validated. The API is available at https://github.com/ga4gh/mme-apis., (© 2015 WILEY PERIODICALS, INC.)

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. Three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow., (© 2015 WILEY PERIODICALS, INC.)

The discovery of disease-causing mutations typically requires confirmation of the variant or gene in multiple unrelated individuals, and a large number of rare genetic diseases remain unsolved due to difficulty identifying second families. To enable the secure sharing of case records by clinicians and rare disease scientists, we have developed the PhenomeCentral portal (https://phenomecentral.org). Each record includes a phenotypic description and relevant genetic information (exome or candidate genes). PhenomeCentral identifies similar patients in the database based on semantic similarity between clinical features, automatically prioritized genes from whole-exome data, and candidate genes entered by the users, enabling both hypothesis-free and hypothesis-driven matchmaking. Users can then contact other submitters to follow up on promising matches. PhenomeCentral incorporates data for over 1,000 patients with rare genetic diseases, contributed by the FORGE and Care4Rare Canada projects, the US NIH Undiagnosed Diseases Program, the EU Neuromics and ANDDIrare projects, as well as numerous independent clinicians and scientists. Though the majority of these records have associated exome data, most lack a molecular diagnosis. PhenomeCentral has already been used to identify causative mutations for several patients, and its ability to find matching patients and diagnose these diseases will grow with each additional patient that is entered., (© 2015 WILEY PERIODICALS, INC.)

We have developed PhenoTips: open source software for collecting and analyzing phenotypic information for patients with genetic disorders. Our software combines an easy-to-use interface, compatible with any device that runs a Web browser, with a standardized database back end. The PhenoTips' user interface closely mirrors clinician workflows so as to facilitate the recording of observations made during the patient encounter. Collected data include demographics, medical history, family history, physical and laboratory measurements, physical findings, and additional notes. Phenotypic information is represented using the Human Phenotype Ontology; however, the complexity of the ontology is hidden behind a user interface, which combines simple selection of common phenotypes with error-tolerant, predictive search of the entire ontology. PhenoTips supports accurate diagnosis by analyzing the entered data, then suggesting additional clinical investigations and providing Online Mendelian Inheritance in Man (OMIM) links to likely disorders. By collecting, classifying, and analyzing phenotypic information during the patient encounter, PhenoTips allows for streamlining of clinic workflow, efficient data entry, improved diagnosis, standardization of collected patient phenotypes, and sharing of anonymized patient phenotype data for the study of rare disorders. Our source code and a demo version of PhenoTips are available at http://phenotips.org., (© 2013 WILEY PERIODICALS, INC.)

Mucopolysaccharidosis II (Hunter syndrome) is a rare x-linked disorder caused by a deficiency in the lysosomal enzyme iduronate-2-sulphatase, leading to an accumulation of the glycosaminoglycans (GAGs) dermatansulphate and heparan sulphate. The consequence of GAGs accumulation is progressive, multiorgan disease. Enzyme-replacement therapy is hypothesised to result in disease stabilisation and improved prognosis. We present a severe case of Hunter syndrome diagnosed at age 2 years and 4 months, who started enzyme-replacement therapy at the age of 3 years and 3 months. We report his evolution after 1 year of treatment. The treatment response was good and there was significant improvement in the quality of life. Owing to the rarity of Hunter syndrome, the multisystem nature and the heterogeneity of disease progression, patient care implies interdisciplinary consultations with a wide range of specialists. The best management can be provided in reference centres for metabolic diseases.

Background/aims: Mutations in the inwardly-rectifying K(+)-channel KCNJ10/Kir4.1 cause autosomal recessive EAST syndrome (epilepsy, ataxia, sensorineural deafness and tubulopathy). KCNJ10 is expressed in the distal convoluted tubule of the kidney, stria vascularis of the inner ear and brain glial cells. Patients diagnosed clinically with EAST syndrome were genotyped and mutations in KCNJ10 were studied functionally., Methods: Patient DNA was amplified and sequenced, and new mutations were identified. Mutant and wild-type KCNJ10 constructs were cloned and heterologously expressed in Xenopus oocytes. Whole-cell K(+) currents were measured by 2-electrode voltage clamping and channel expression was analysed by Western blotting., Results: We identified 3 homozygous mutations in KCNJ10 (p.F75C, p.A167V and p.V91fs197X), with mutation p.A167V previously reported in a compound heterozygous state. Oocytes expressing wild-type human KCNJ10 showed inwardly rectified currents, which were significantly reduced in all of the mutants (p < 0.001). Specific inhibition of KCNJ10 currents by Ba(2+) demonstrated a large residual function in p.A167V only, which was not compatible with causing disease. However, co-expression with KCNJ16 abolished function in these heteromeric channels almost completely., Conclusion: This study provides an explanation for the pathophysiology of the p.A167V KCNJ10 mutation, which had previously not been considered pathogenic on its own. These findings provide evidence for the functional cooperation of KCNJ10 and KCNJ16. Thus, in vitro ascertainment of KCNJ10 function may necessitate co-expression with KCNJ16., (© 2013 S. Karger AG, Basel.)

Purpose: Repeated administration of low-dose silver nitrate (SN) has been shown to be effective in creating pleurodesis. This study aimed to determine the effectiveness of a SN-eluting pleural catheter for pleurodesis., Methods: Catheters with a chitosan-SN-hyaluronic acid hydrogel coating designed to release SN over 14 days, or placebo uncoated catheters, were inserted in rabbit and lamb pleurodesis models. Pleurodesis was assessed at 28 days according to a 1-8 point scoring system and pleural fibrosis and inflammation assessed histologically on a 0-4 point scale., Results: In the rabbit model, pleurodesis scores were significantly increased in both the 24 mg and 50 mg SN catheters versus control animals as well as compared to the contralateral untreated pleural space (median-treated side scores were 5, 8, and 1, respectively, median score for contralateral side was 1 in all groups). In the lamb model, pleurodesis scores were significantly increased in both the 750 mg and 1000 mg catheter groups versus control animals as well as compared to the contralateral untreated pleural space (median-treated side scores were 7, 7, and 1, respectively, median score for contralateral pleural space was 1 in all groups). Catheters appeared well tolerated, although higher than expected mortality was seen in the 50 mg catheter rabbit group., Conclusions: A catheter designed to deliver SN to the pleural space over 14 days appears to be effective in creating pleurodesis. Further investigations to determine in-vivo catheter pharmacokinetics, toxicity, dose and optimal coating methods are warranted.

The relationship between different species of oral Treponemas and inflammation in periodontal disease progression is complex. The purpose of this study was to analyze and compare the subgingival plaque samples collected from periodontally healthy subjects and from chronic gingivitis and periodontitis patients in order to detect the presence of T. denticola, T. pectinovorum, T. socranskii and T. vincentii using nested-PCR technology. After DNA extraction from the samples using QIAmp DNA Mini Kit (QIAGEN, the four Treponema species were determined with nested-polymerase chain reaction which requires two sets of primers to amplify a specific DNA fragment in two separate runs of PCR. Pearson chi-square was implemented to compare the three groups as to the presence of four Treponema species. Results of this investigation showed significant differences between groups regarding subject proportion of T. denticola, T. socranskii, T. pectinovorum, T. vincentii, with a higher percentage of patients from associated-disease groups of patients harboring these four species than healthy subjects. These differences were more pronounced in presence of Treponema denticola and Treponema socranskii. Our findings suggest that Treponema denticola and Treponema socranskii concurrent presence indicate more accurately the association with chronic gingivitis and periodontitis.

Unlabelled: The aim of this study was to isolate and identify at species level the strains of anaerobic Gram-negative bacilli (GNB) from pus samples collected in patients with abscesses of fascial spaces of the face and neck. Microscopy of Gram-stained smears and cultures were performed in each specimen. The strictly anaerobic GNB strains were identified using the conventional methods of diagnosis and the Rapid ID 32 A system. In addition, the other strains isolated in association with these bacteria were identified at least to genus level. The 28 anaerobic GNB isolates belonged to: Fusobacterium nucleatum and different species of Prevotella (4 species) and Bacteroides (3 species)., Conclusions: The anaerobic GBN strains were recovered--either alone or in association with other migroorganisms--in more than half of all investigated samples and represented about 40% of all isolates. The most frequently isolated species were P> melaninogenica and B. ureolyticus.

The aim of this study was to identify at species level and to investigate the antibiotic susceptibility of oral streptococcal strains isolated from 100 pus samples collected from Romanian patients with different odontogenic infections. The isolates were identified at species level using the Rapid ID 32 STREP system and their susceptibility was testing by the Etest, against: penicillin G, ampicillin, erythromycin, clindamycin and tetracycline. For the investigation of erythromycin resistance phenotype the disk diffusion test was used. The isolates belonged to several species, with Streptococcus anginosus and Streptococcus oralis predominating. Reduced susceptibility to beta-lactam antibiotics was found only among the isolates belonging to S. mitis and S. sanguinis groups. Resistance to erythromycin was detected among all species, except for: S. constellatus, S. intermedius and S. gordonii, and the M phenotype was established, while resistance to tetracycline was detected within all species but S. gordonii. In contrast, clindamycin was fully active. As most odontogenic infections are mixed infections, often involving strictly anaerobic bacteria, which are frequently beta-lactamase producers, the association of a penicillin and a beta-lactamase inhibitor, like Amoxiclav, is recommended when the antimicrobial treatment is necessary.

The aim of the present study was to identify at species level and to characterize the strains of streptococci belonging to anginosus group isolated from 30 pus samples collected from patients with abscesses of fascial spaces of the face or neck. The identification of facultatively anaerobic Gram-positive cocci in chains at genus level was made by conventional diagnosis methods and at species level by the help of Rapid ID 32 STREP system. The cultural, biochemical and antigenic (limited at Lancefield Group identification by Slidex Strepto-Kit) characterization was performed in the mean time with the species identification. The anginosus streptococcal strains were isolated either in association with other bacteria or in pure culture and S. anginosus isolates clearly predominated. As expected, the anginosus streptococcal strains were found to be heterogeneous regarding the cultural, biochemical and antigenic features.

The aim of the study was to identify at species level the Prevotella strains from 30 pus samples collected by needle aspiration in patients with abscesses of fascial spaces of the face and neck. Microscopy of Gram-stained direct smear and cultures on selective and nonselective media incubated aerobically and anaerobically were performed in each pus specimen. All strains of Gram-negative strictly anaerobic bacilli were identified to genus and species level using conventional methods of diagnosis and the Rapid ID 32 A system (BioMérieux, Marcy-l'Etoile, France). The Prevotella isolates were recovered (alone or in association with other bacteria) in 46.6% of the investigated specimens and were represented in reverse order of frequency by the following species: P. melaninogenica, P. denticola, P. oralis and P. loescheii. In conclusion, the rate of Prevotella isolation was relatively high and the most frequently isolated species was P. melaninogenica (followed by P. denticola), while no P. intermedia was found.

Background & Objectives: Suppurative oral and maxillofacial infections are usually mixed infections due to aerobic and anaerobic bacteria, most frequently by oral streptococci and antimicrobial treatment is necessary for such infections. The aim of this study was to investigate the antimicrobial susceptibility of Streptococcus mitis group strains isolated from Romanian patients with different oral and maxillofacial infections., Methods: Eighty-five isolates belonging to S. mitis group isolated from pus samples were identified at species level by the Rapid ID 32 STREP system. The E test was used to determine the susceptibilities of the isolates to penicillin, ampicillin, cefotaxime, erythromycin, clindamycin, chloramphenicol and tetracycline., Results: Of the 151 samples studied, 85 isolates belonged to S. mitis group. The minimum inhibitory concentration (MIC) values (mg/l) ranged from 0.016-0.75 for penicillin, 0.016-2 for ampicillin, 0.016- 1 for cefotaxime, 0.016-4 for erythromycin, 0.016-0.047 for clindamycin, 0.5-4 for chloramphenicol and 0.047-256 for tetracycline., Interpretation & Conclusion: The low susceptibility and the resistance to some commonly used antibiotics found in this study indicated a need for a careful surveillance of the susceptibility pattern of oral streptococci isolates of clinical significance. Clindamycin and chloramphenicol might be suitable alternative agents in treatment of oral and maxillofacial infections involving penicillin-resistant bacteria and in case of patients with hypersensitivity to beta-lactam antibiotics.

Lipases were noncovalently immobilized in Chitoxan, a polyionic hydrogel obtained by complexation between chitosan and xanthan. The properties of free and immobilized lipases have been compared. In the aqueous medium, the activity was twice as high for immobilized lipases as for free lipases. Immobilized lipases in chitoxan were able to hydrolyze triacylglycerols in three distinct organic solvent media. At the microstructural level, lipases were not distributed uniformly in the chitoxan beads. Higher concentrations of lipase were found in the outer membrane-like layer of the beads, as compared with lower concentrations in the inner part of the beads.

Microspheres of a polyelectrolyte complex hydrogel were prepared from chitosan and xanthan after interaction between the two polyionic polymers. Their biodegradation was studied vs. chitosan. Simulated gastric fluid (SGF, pH 1.2) and intestinal fluid (SIF, pH 7.5) both as biodegradation media and phosphate buffered saline (PBS, pH 7.4) as a negative control were used. The degradation studies were performed at 37 degrees C at 240 rpm permanent stirring to mimic the physiologic conditions. High performance liquid chromatography (HPLC) was carried out to quantify the chitosan degradation products using glucosamine (GA) and N-acetyl-D-glucosamine (N-Ac-GA) as references. The peaks area integration method was used to determine the amount of each degradation product as a function of incubation time in the media. The effect of the media on the morphological structure of microspheres was assessed by scanning electron microscopy. From HPLC studies, it appeared that in SGF and SIF the major degradation products were glucosamine (GA) and N-acetyl-D-glucosamine (NAc-GA). In the first 15 days, oligochitosan fractions were released from the complex, whereas N-acetyl-D-glucosamine was detected in the media after this period. The degradation kinetics were assessed by the measurement of the cumulative degradation products, which showed faster degradation of chitosan than the complex in SGF and SIF. SEM micrographs showed an enhancement of microsphere porosity as a function of incubation time in the simulated physiological media. Our results suggest a better control of the degradation kinetics when chitosan is complexed to xanthan., (Copyright 2000 John Wiley & Sons, Inc.)

A novel hydrogel, CHITOXAN(TM) (CH-X), has potential as a vehicle for controlled drug delivery. The hydrogel is obtained by complexation of two polysaccharides, chitosan and xanthan. In the present work we investigated the biocompatibility of the complex using in vitro and in vivo models. The cytotoxic effects of CH-X microspheres as well as their degradation products at different concentrations were assessed on fibroblasts (fibroblast cell line L-929) using 3-(4,5-dimethylthiazole-2yl)-2,5-triphenyl tetrazolium) (MTT). The test is based on mitochondrial dehydrogenase cell activity as an indicator of cell viability. Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) cytokines as well as nitric oxide (NO) production by macrophages (macrophage cell line J-774) were examined as indicators of cell activation. In vivo biocompatibility assessment was performed for 1 to 12 weeks. This study was performed using tablets obtained after compression of CH-X particles implanted at the subcutaneous level in male Wistar rats. CH-X biocompatibility and degradation were investigated using histological studies. Light and transmission electron microscopy (TEM) analyses were used to determine the foreign-body reaction and phagocytosis of the implants by macrophages. Fibroblast exposition to CH-X particles and degradation products did not show cytotoxic effects as measured by MTT test. TNF-alpha production was dependent on CH-X particles concentration, whereas IL-1beta production was found to be dose independent. CH-X extract products stimulated TNF-alpha secretion when used at the highest concentration (10 mg/mL), notably after 28 days' degradation time. No effect was observed on IL-1beta production when CH-X extracts were used in comparison to the control. The effects of CH-X particles on NO secretion were similar as on TNF-alpha. Histological studies showed that CH-X tablets broke down into particles which progressively degraded into smaller fragments. A significant fraction of the fragments was ingested by the macrophages after 12 weeks of implantation. Light microscopy studies showed a weak foreign-body reaction as a function of time and the fibrous layer thickness decreased with time of implantation., (Copyright 2000 John Wiley & Sons, Inc.)

The aim of the study was to isolate and identify at species level streptococci strains of anginosus group in pus samples collected from 110 patients with oral and maxillofacial (OMF) infections. Gram-stained smears and cultures on selective and nonselective media were done from each of the 111 pus samples (2 samples were collected from one of the patients, who presented 2 oral abscesses at the same time). The isolates were identified on the basis of cultural and biochemical characteristics. Speciation of the anginosus group isolates was performed using the Rapid ID 32 Strep system (Bio Mérieux, France). Fourty-four anginosus group strains were isolated from 42 patients. Fourty of these isolates were identified as Streptococcus anginosus (2 nonidentical isolates were found in 2 patients), 3 isolates as Streptococcus constellatus and only one as Streptococcus intermedius. The study confirmed that the anginosus group is often involved in OMF infections alone or in association with other aerobic and/or anaerobic bacteria. In the investigated cases, Streptococcus anginosus was by far the most frequently isolated species within the anginosus group.

Streptococci strains of the anginosus group isolated from various oral and maxillofacial infections (OMF) were screened for their susceptibility to the following antimicrobial agents: benzylpenicillin, ampicillin, oxacillin, cephalothin, ceftazidime, cefotaxime, cefuroxime, erythromycin, clindamycin, tetracycline, chloramphenicol, vancomycin and trimethoprime-sulphamethoxazole. The isolates were susceptable to: clindamycin, chloramphenicol, vancomycin and all beta-lactam antibiotics, except ceftazidime to which 54.5% of the strains showed intermediate susceptibility. Intermediate susceptibility to tetracycline was found in 11.3% of the strains, whereas resistance to the same antibiotic was demonstrated in 61.4%. Resistance to erythromycin and trimethoprime-sulphamethoxazole was of 2.3% for both. In conclusion, penicillin is the drug of choice in infections caused by streptococci of the anginosus group.

The notion of a polyelectrolyte complex is well established for the complexation of two polymers one anionic, the other cationic. Electronic microscopy studies have shown the formation of a fibrilar structure. A method for the preparation of polyionic hydrogels from the complexation of chitosan and xanthan is reported. Electronic microscopy studies have shown the formation of a fibrilar structure. Stable hydrogels have been used to immobilize xylanase, lipase and protease. The immobilized xylanase and lipase activity was significantly higher than that of the free enzyme.

The aim of this study was to briefly characterize serologically, biochemically and from the cultural point of view some anginosus group isolates found in pus samples collected from patients with oral and maxillofacial infections. Cultural characterization was done by studying the culture odor, the colony size and aspect, and hemolysis type on Columbia bood agar (BA). Lancefield grouping was made on cards using the rapid latex-agglutination test (Slidex Strepto-Kit, Bio Mérieux, France). The biochemical characterization was performed at the same time with the speciation by the Rapid ID 32 Strep system (Bio Mérieux, Marcy-l'Etoile, France). The anginosus group isolates were phenotypically heterogenic. Based on phenotypic description, nonidentical anginosus group isolates were found in the same patient sample.

The aims of the study were to isolate and to identify at species level the Prevotella strains in pus samples collected by needle aspiration from 25 Romanian patients with periodontal abscesses. Gram-stained smears and cultures on selective and nonselective media were performed from each of the 25 pus samples. The isolates were identified on the basis of Gram staining, cultural characteristics and standard biochemical reactions. The Gram-negative anaerobic bacilli isolates were biochemically characterized and identified at species level using the Rapid ID 32 A system (Bio Mérieux, France). Fifteen Prevotella isolates belonging to one of the following species: P. melaninogenica, P. denticola, P. oralis, P. loescheii and P. bivia were recovered. All Prevotella isolates reacted similarly in 20 tests in the Rapid ID 32 A system. The P. melaninogenica strain showed approximately the same biochemical profile and only two sugar fermentation tests were not constantly positive. The study confirmed that Prevotella is often involved in periodontal abscesses (> 50% of the cases) in association with other anaerobic or/and aerobic bacteria. P. melaninogenica was the most frequently isolated Prevotella species from the investigated cases.

The present paper studies the process of esterification of nalidixic acid on poly(vinyl alcohol). The influence of time, dilution and concentration of the reactants on the efficiency of esterification with dicyclohexylcarbodiimide has been followed. By experiment scheduling according to a centered, rotatory, compound, second order program, optimum conditions for the system under study have been found. On the other hand, the evolution of reaction of esterification of the nalidixic acid on poly(vinyl alcohol) was followed by using the activator-catalyst (4-pirolidinopyridine) system. An increase of the esterification yield up to 37% has been observed.

The neomycin-furazolidone-xanthan complex has been synthesized. Neomycin is covalently linked to xanthan, while furazolidone is inserted in the hydrogel formed by the reaction between neomycin and xanthan. The content of neomycin and furazolidone depends on the drug rate in the reaction medium. Thus, a zero-order kinetics is obtained for the release of both neomycin and furazolidone in basic medium. The complex's antimicrobial activity is intensified.

The paper studies the coupling reaction by covalent bonding of acetylamino-2-sulfamoyl-1,3,4-thiodiazole (AcAA) on the poly(acrylic acid-costyrene) copolymer (PAcA-S) in homogeneous system, in the presence of dicyclohexylcarbodiimide (DCC) as activator. The influence of some factors on coupling efficiency (the drug/support ratio, time, volume of solvent), as well as the mathematical model correlating the amount of coupled drug with these parameters is established. Maximum amounts of drug (28%) are chemically bound when employing maximum values of the parameters mentioned (i.e., AcAA/PAcA-S ratio = 2 mole/mole; time = 50 h; THF volume = 60 ml). Physicochemical and spectral analyses evidence the existence of some chemical bonds of the -CO-NH-SO2-type between the macromolecular support and the drug. In vivo tests have demonstrated the gradual hydrolysis of the chemical bonds as well as the release of the drug, due to the diuretic effect produced.

Neomycin is coupled on xanthan--a polysaccharide of microbial biosynthesis produced by Xanthomona campestris--through ionic complexation. The kinetics of neomycin release, in vitro, at pH = 8.2 is studied. A release of neomycin, following a zero order kinetics, is observed, regardless of the eluent flow-rate. The neomycin-xanthan complex, protected by a cellulosic membrane, behaves like a monolithic-type device. Diffusion coefficients--increasing with increasing the eluent flow-rate--are also calculated.

Neomycin is coupled on xanthan-a polysaccharide of microbial biosynthesis produced by Xanthomonas campestris-through ionic complexation. The kinetics of neomycin release, in vitro, at pH = 8.2 is studied. A controlled release of neomycin, following a zero order kinetics is observed, regardless of the eluent flow. Neomycin complexed on xanthan, administered in a unique daily dose to patients suffering from dysentery in the 100 cases taken in study, has shown a high clinical efficiency as compared with the treatments with ampicillin or furazolidone, administered for 5-10 days or longer.

Xanthan has been reticulated with epichlorohydrin to obtain a hydrogel for use in drug retardation. The obtained gel shows swelling degrees up to 1000. Theophylline has been inserted by diffusion into this gel; concentrations around 150 mg theophylline/g dry hydrogel being obtained. Controlled release of theophylline has been established by elution in a close recirculation system. Zero-order kinetics has been obtained in the diffusion process of theophylline into the eluent, within a 14 h time interval.

Modified neomycin prepared by the ionic coupling on xanthan with an activity of 380 UI/mg was characterized in regard to its in vitro and in vivo release rate and therapeutic action with artificial tear eluent. The dynamic system in vitro release showed that after 4 h, there appears a "zero-order" kinetic. Ophthalmic inserts were prepared from modified neomycin and they are used in treating bacterial conjunctivitis. Sterilization of the conjunctival sac is obtained 12 h after insert administration.

One of the current question in this field is that of the possibility for parodontal disease to be an autoimmune disease. There is no clear answer as yet in the specialized literature, and no coherent and complete concepts. Starting from the existing data the authors have carried out immunological studies in patients with parodontal disease, considering the chronic, recidivating aspects of this disturbance, even after a complex therapy, and removal of pathological structures. They attempted to investigate the autoimmune components of the disease, and have employed immunofluorescent techniques of the indirect type for the study of gingival fragments without lesions obtained from patients with parodontopathies. The data obtained have demonstrated, besides the presence at the surface of the epithelium of stable immune complexes, that could be the effect of bacterial antigenic material, and cell fluorescence in the epithelium and the chorion, a fluorescence that was superposed on the respective tissue architecture. These data suggest implication of autoimmune mechanism in parodontal disease, and can explain, in the frame of the clinical aspects of chronic marginal parodontopathies, the auto-aggressive character, and the self-maintenance of these processes in certain conditions, even when an adequate therapy has been applied.

Invertase was immobilized on diazotized 4-aminobenzoylcellulose. The optimum coupling conditions, namely enzyme concentration, time, and pH, were determined. The temperature and pH value for the maximum activity of the immobilized enzyme were determined and the apparent Michaelis constant was estimated.

This article reports on the reaction of urease immobilization through its covalent bonding on carboxymethylcellulose. The reaction is activated by dicyclohexylcarbodiimide. The coupling reaction is influenced by the enzyme-support and activator-support ratios, as well as by duration. Starting from a rotating, composed experimental program of the second order, the function correlating the activity of the immobilized enzyme with the reaction parameters is established. Immobilized urease exhibits thermal stability higher than that of free enzyme, regarding both pH and the inhibiting action of some metal ions or organic substances. The stability over time of the immobilized urease is high, its enzymatic activity being maintained at over 85% of the initial value three months after synthesis.

The kinetics of delayed release neomycin-xanthan complex, and its antimicrobial activity, were studied. Delayed release neomycin (53.13% free neomycin) had zero-order release kinetics, when artificial tear solution was used as eluent. Microbiological tests revealed an activity of 380 units/mg, 10% higher than neomycin in its free form.

Passive haemagglutination test with pathogenic Treponema pallidum antigen in the serodiagnosis of syphilis, carried out on 752 sera (518 syphilitic patients and 234 subjects without evidence of syphilis) showed a greater general sensitivity as compared the cardiolipin tests and complement fixation test with Reiter protein antigen, and lower, to immunofluorescence (FTA--ABS). Its specificity is relatively lower than that of the cardiolopin and treponemal tests. Associated with the cardiolipin test it may be preferably used for the detection of syphilis, and moreover, passive haemagglutination may confirm the diagnosis in case of weak positive results with the FTA--ABS test. The latter is, however, essential for problem cases.

The paper presents results obtained by the treatment of chronic marginal parodontopathies with natural products of apiarian derivatives and vegetal extracts. These are original preparations such as Proparodont, sage extracts, watercress extracts, etc., by comparison with other similar existing products, and with zinc chloride. The clinical study evaluated the "inflammation status of the marginal prodontium" on the basis of variations in the PMA index. The microbiological study has established the bacteriostatic and the bactericidal activities of the products employed. The results obtained stress the high antimicrobial activity of the original products called Proparodont, and stress its antimycotic effects, especially against Candida albicans. The blackwort (Symphytum off.) extracts have a good repair effect, especially after surgical procedures. The complex original products based on propolis and vegetal extracts are indicated in the treatment of inflammatory lesions of the gingivo-parodontal tissues, and of the buccal mucosa. They also have antimicrobial effects, as well as antimycotic, antiinflammatory and antiscar effects. They de not have side effects which are characteristic for other medicinal drugs employed in the treatment of chronic marginal parodontopathies.

The coupling of chloramphenicol on Biozan R (Hercules) by activation with dicyclohexylcarbodiimide was studied. The esterification is influenced by the chloramphenicol/dicyclohexylcarbodiimide ratio, concentration of the reactants and reaction time. The Biozan R-chloramphenicol system containing 15% chloramphenicol was used to obtain ophthalmic ointments. They were studied from the point of view of their physicochemical and biological properties. Tests were performed on animals and volunteers to establish the ophthalmic tolerance; some clinical observations on treated eyes were also made.