Efficacy of quaternary ammonium salt-based disinfectant or chelated copper-zinc footbath solution in the treatment of digital dermatitis on one research dairy farm in Taiwan.

BACKGROUND: Footbaths can be used to manage digital dermatitis (DD), a common cause of lameness in dairy cattle. Copper sulfate and chelated copper-zinc (CZS) solutions in footbaths are potentially harmful to the environment. HYPOTHESIS/OBJECTIVES: To determine if a quaternary ammonium salt-based disinfectant (QASD) footbath is as effective as a chelated CZS solution in controlling DD in dairy cows. ANIMALS: Fifty-one lactating Holstein cows were randomly assigned to one of two treatment groups, with DD status based on the M-stage scoring system and locomotion score balanced between treatment groups. MATERIALS AND METHODS: The groups were treated with a 1% QASD or a 2.5% chelated CZS. Footbaths were performed once per week for 15 weeks. Logistic regression was used to analyse clinical improvement. All cows received appropriate medical treatment for DD and other hoof diseases. RESULTS: Clinical improvement rates were 67% in the QASD group and 38% in the CZS group (p = 0.03). Logistic regression analysis showed that the odds (95% confidence interval) for clinical improvement rate in the CZS group were 0.30 (0.095-0.948) times that of the QASD group (p = 0.04). The M0 score in the QASD and CZS groups increased significantly (p < 0.05) at the end of the 15 week study period. In the QASD group, the proportion of M2, M3 and M4 scores were significantly decreased (p < 0.05). CONCLUSION AND CLINICAL RELEVANCE: Over a 15 week period, QASD for footbathing was associated with a lower prevalence of active DD lesions than when using CZS.

Real-time gastric juice analysis with EndoFaster for H. pylori diagnosis: a large, multicentre study.

BACKGROUND: Helicobacter pylori infection is the main cause of the most frequent gastroduodenal diseases. Because its prevalence is decreasing in developed countries, gastric biopsies are negative in several patients. By measuring ammonium in the gastric juice, EndoFaster allows to exclude H. pylori infection during endoscopy. This study aimed to assess the accuracy of device versions working with either 6 ml or 3 ml of gastric juice. STUDY DESIGN: This prospective study involved 12 endoscopic units. During endoscopy, EndoFaster testing was performed and standard five gastric biopsies were taken. The accuracy was calculated by considering histological assessment as the gold standard for H. pylori diagnosis. RESULTS: Gastric juice analysis was attempted in 1279 patients, but it failed in 131 (15.5%) and in 10 (2.3%), with the 6 ml and the 3 ml device, respectively (P &lt; 0.001). Overall, EndoFaster detected H. pylori infection with an 86.3% sensitivity, 83.3% specificity, 52.7% positive predictive value, 96.6% negative predictive value and 83.8% accuracy. The performance was not affected either by ongoing proton pump inhibitor therapy or a previous H. pylori eradication. No significant difference in accuracy emerged between the two versions of the device. CONCLUSION: The novel version of the EndoFaster device operating with 3 ml gastric juice may be performed in virtually all patients, and it allows excluding H. pylori infection with a very high accuracy. Gastric biopsies can be avoided in a definite portion of cases without endoscopic lesions or other clinical indications.

Real-time determination of gastric juice pH with EndoFaster® for atrophic gastritis assessment.

BACKGROUND: In patients with atrophic gastritis involving gastric body mucosa the pH value of gastric juice is distinctly increased, so that pH assessment would allow predict this precancerous lesion. We tested whether EndoFaster® - a device allowing real-time pH measure and H. pylori diagnosis - may optimize the need of taking gastric biopsies. METHODS: In this prospective, multicentre study, the accuracy of EndoFaster® for ruling out gastric atrophy involving corporal mucosa was assessed. Real-time pH and ammonium determination was performed by aspirating 3-6 ml gastric juice during endoscopy. Histology performed on 5 standard gastric biopsies was used as gold standard. RESULTS: A total of 1008 consecutive patients were observed in 12 centres. At histology, gastric body mucosa atrophy/metaplasia was detected in 65 (6.4%) cases, and a pH value >4.5 in the gastric juice was observed in 150 patients. The values of EndoFaster® performance in predicting the presence of atrophic gastritis were as follow: 51% sensitivity, 84% specificity, 18% PPV, 96% NPV, and 82% accuracy. The NPV value was not distinctly affected by neither ongoing proton pump inhibitor therapy nor H. pylori infection. By considering also data of ammonium concentrations, the values of EndoFaster® in detecting extensive atrophy on gastric mucosa were 74% sensitivity, 84% specificity, 24% PPV, 98% NPV, and 83% accuracy. CONCLUSION: The very high NPV of EndoFaster® might allow to safely rule out presence of atrophic gastritis, reducing the need of taking gastric biopsies in unselected patients managed in clinical practice.

IgD lambda multiple myeloma causing hyperammonaemia with possibly reduced ammonium excretion.

A man in his 70s presented with impaired consciousness due to hyperammonaemia while investigating multiple tumours in his brain, chest, spine and right adrenal gland. He did not have any disorders causing hyperammonaemia, such as liver dysfunction, urea-producing bacterial infection or any medications interfering with ammonium metabolism. Blood and urine tests in addition to tumour biopsy specimens confirmed immunoglobulin D lambda multiple myeloma. His general status responded to chemotherapy using bortezomib, dexamethasone and daratumumab, and he subsequently regained full consciousness and a normalised serum ammonia level. He, unfortunately, died of refractory multiple myeloma with hyperammonaemia. The autopsy specimen revealed lambda light-chain deposits in the distal tubule epithelium with cast precipitation and intact liver cells. Urine osmolality gap analysis suggested possibly reduced urinary ammonium excretion, but further investigation is necessary to elucidate the significance of pathological renal characteristics in multiple myeloma with hyperammonaemia.

The effect of sodium zirconium cyclosilicate on acid-base balance in chronic kidney disease.

Hyperkalemia is a common electrolyte abnormality in chronic kidney disease (CKD). Sodium zirconium cyclosilicate (SZC) is a novel selective cation exchanger that is used to treat hyperkalemia and may also capture ammonium, which is of a similar size to potassium. We investigated the effect of SZC on acid-base balance in CKD patients. This retrospective study surveyed 20 patients with CKD whose serum potassium levels were maintained within the normal range by treatment with polysulfonate resin, which was replaced with SZC during the clinical course. We compared clinical parameters before and after changing medications. Changing the potassium binder from polysulfonate resin to SZC increased serum bicarbonate (p = 0.016) and decreased blood urea nitrogen (p = 0.017). Serum potassium levels were maintained within the normal range. Urine pH, anion gap, and osmolality gap were unchanged during treatment. No gastrointestinal symptoms were noted during the observation period. Our data suggest that SZC may improve not only hyperkalemia but also metabolic acidosis by increasing the excretion of ammonium from the intestinal tract in patients with CKD. SZC could be a more suitable medication for CKD patients with hyperkalemia and metabolic acidosis.

Mechanisms of ammonium-induced neurotoxicity. Neuroprotective effect of alpha-2 adrenergic agonists.

Here we report the effects of ammonium on the main biophysical features of neurons and astrocytes during the first minutes of exposure. We found that ammonium causes the depolarization of neurons, which leads to the generation of high-frequency action potentials (APs). The initial alkalization and subsequent acidification of the intracellular medium in neurons occur along with the generation of calcium oscillations. Moreover, although the kinetics of calcium response of neurons and astrocytes is different, the dynamics of changes in the intracellular pH (pHi) is similar. The rate of superoxide production and mitochondrial membrane potential do not change in most neurons and astrocytes during ammonium exposure. At the same time, we observed an increased superoxide production and a decrease in the mitochondrial potential in some neurons in response to ammonium application. However, in both cases, the amplitude of the calcium response in these neurons is significantly higher compared to other neurons. Application of UK 14,304, an agonist of alpha-2 adrenergic receptors (A-2ARs), decreased the frequency of APs upon ammonium-induced high-frequency spike activity. Moreover, we also observed periods of hyperpolarization occurred in individual neurons. We suppose that this hyperpolarization contributes to the suppression of activity and can be mediated by astrocytic GABA release, which is stimulated upon activation of A-2ARs. Thus, our findings reveal a new possible mechanism of the protective action of alpha-2 adrenergic agonists against ammonium-induced hyperexcitation and demonstrate the correlation between intracellular calcium concentration, mitochondrial membrane potential, pHi, the intensity of superoxide production in hippocampal cells under acute hyperammonemia.

Simple ammonium salts acting on sigma-1 receptors yield potential treatments for cancer and depression.

Sigma-1 and sigma-2 receptors are emerging therapeutic targets. We have identified that simple ammonium salts bind to these receptors and are effective in vivo. Radioligand binding assays were used to obtain structure-activity relationships of these salts. MTS assays were performed to determine their effect on growth in MCF7 and MDA-MB-486 cells. Anticancer properties were tested in NMRI mice transplanted with a fragment of mouse adenocarcinoma (MAC13). Antidepressant activity was tested using the forced-swim test and tail suspension tests. Dipentylammonium (Ki 43 nM), tripentylammonium (Ki 15 nM) and trihexylammonium (Ki 9 nM) showed high affinity for the sigma-1 receptor. Dioctanoylammonium had the highest affinity (K50 0.05 nM); this also showed the highest affinity for sigma-2 receptors (Ki 13 nM). Dipentylammonium was found to have antidepressant activity in vivo. Branched-chain ammonium salts showed lower affinity. Bis(2-ethylhexyl)ammonium (K50 29 µM), triisopentylammonium (K50 196 µM) and dioctanoylammonium showed a low Hill slope, and fitted a 2-site binding model for the sigma-1 receptor. We propose this two-site binding can be used to biochemically define a sigma-1 receptor antagonist. Bis(2-ethylhexyl)ammonium and triisopentylammonium were able to inhibit the growth of tumours in vivo. Cheap, simple ammonium salts act as sigma-1 receptor agonists and antagonists in vivo and require further investigation.

Use of silver diamine fluoride for dental caries management in children and adolescents, including those with special health care needs

BACKGROUND: This manuscript presents evidence-based guidance on the use of 38 percent silver diamine fluoride (SDF) for dental caries management in children and adolescents, including those with special health care needs. A guideline workgroup formed by the American Academy of Pediatric Dentistry developed guidance and an evidence-based recommendation regarding the application of 38 percent SDF to arrest cavitated caries lesions in primary teeth. TYPES OF STUDIES REVIEWED: The basis of the guideline's recommendation is evidence from an existing systematic review "Clinical trials of silver diamine fluoride in arresting caries among children: A systematic review." (JDR Clin Transl Res 2016;1[3]:201-10). A systematic search was conducted in PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and gray literature databases to identify randomized controlled trials and systematic reviews reporting on the effect of silver diamine fluoride and address peripheral issues such as adverse effects and cost. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of the evidence and the evidence-to-decision framework was employed to formulate a recommendation. RESULTS: The panel made a conditional recommendation regarding the use of 38 percent SDF for the arrest of cavitated caries lesions in primary teeth as part of a comprehensive caries management program. After taking into consideration the low cost of the treatment and the disease burden of caries, panel members were confident that the benefits of SDF application in the target populations outweigh its possible undesirable effects. Per GRADE, this is a conditional recommendation based on low-quality evidence. Conclusions and practical implications: The guideline intends to inform the clinical practices involving the application of 38 percent SDF to enhance dental caries management outcomes in children and adolescents, including those with special health care needs. These recommended practices are based upon the best available evidence to-date. A 38 percent SDF protocol is included in Appendix II.

Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma.

PURPOSE: This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox). METHODS: A quaternary ammonium derivative of the MMP13 inhibitor doxycycline (QA-Dox) was synthesized, and its anticancer activity was evaluated in the Swarm rat chondrosarcoma (SRC) model compared with the parent drug doxycycline, in vitro and in vivo. In vivo, dox and QA-Dox efficiency was assessed at equimolar doses according to a q4dx4 schedule by monitoring tumour volume by MRI and PG-targeted scintigraphy. Molecular mechanism (MMP13 expression, proteoglycan level) and histology studies were performed on tumours. RESULTS: The link of QA targeting function to Dox maintained the MMP13 inhibitory activity in vitro. Interestingly, the bacteriostatic activity was lost. SRC cells incubated with both drugs were blocked in S and G2 M phases. Tumour growth inhibition (confirmed by histology) was observed for both Dox and QA-Dox. Undesirable blood effects (leukocyte decrease) were reduced when Dox was targeted to tumour tissue using the QA function. CONCLUSIONS: In the SRC model, the MMP13 inhibitor Dox and its QA derivative are promising as adjuvant therapies for chondrosarcoma management.

Silk textile with antimicrobial AEM5772/5 (Dermasilk): a pilot study with positive influence on acne vulgaris on the back.

BACKGROUND: The use of special silk textiles (Dermasilk) has shown positive effects on chronic inflammatory diseases like lichen sclerosus et atrophicus, atopic dermatitis, diabetic ulcerations, and vulvovaginal candidiasis. OBJECTIVE: Wearing T-shirts of this particular fabric could be useful in the management of patients with acne vulgaris on the back and trunk. MATERIAL AND METHODS: Dermasilk T-shirts were given to 14 patients with acne vulgaris papulopustulosa on the back. The patients wore these shirts every night for 6 weeks, and their acne lesions were monitored. Dermasilk represents a polymerisate of fibroin, a silk protein, and antimicrobial AEM5772/5, an unsoluble colorless, odorless ammonium with antifungal and antibacterial ability. RESULTS: Photographic documentation before and after 6 weeks showed a clinically significant reduction in acne lesions on the back without any concomitant treatment or change in lifestyle and living conditions. DISCUSSION: The use of Dermasilk textiles in other subacute-chronic inflammatory skin diseases has shown positive effects. This is the first report on their safe and effective use in the management of acne vulgaris papulopustulosa corporis.

Small rigid platforms functionalization with quaternary ammonium: targeting extracellular matrix of chondrosarcoma.

This work takes place in the "cartilage targeting strategy", consisting in using the quaternary ammonium (QA) function as a vector to proteoglycans (PGs) of extracellular matrix (ECM). The objective was to demonstrate that QA could address gadolinium based small rigid platforms (SRP) to PG-rich tumors. SRP were functionalized with QA, radiolabeled with (111)Indium and evaluated for biodistribution in vivo, respectively to non functionalized SRP, in two experimental models: (i) the HEMCSS human xenograft model; (ii) the Swarm rat chondrosarcoma (SRC) orthotopic model. The contribution of cellular uptake to tumoral accumulation of nano-objects was also determined from in vitro binding. In the SRC model expressing a highly and homogeneously distributed PG content, tumor accumulation and retention of SRP@QA were increased by 40% as compared to non-functionalized SRP. When considering the radiosensitizing potential of gadolinium based SRP, these results provide hopes for the radiobiological approach of highly resistant tumor such as chondrosarcoma. FROM THE CLINICAL EDITOR: In this study, gadolinium-based complexing DOTA-surfaced small polysiloxane nanoparticles were functionalized with quaternary ammonium derivatives that target the extracellular matrix of chondrosarcoma. The authors demonstrate in a rat model that the use of these constructs results in a 40% increase of tumor accumulation and retention compared to non-functionalized (and otherwise same) platforms. Similar approaches would be welcome additions to the clinical armamentarium addressing chondrosarcoma.

Efeitos do lactato de amônio tópico sobre a atrofia cutânea causada por um corticosteróide tópico potente / Effects of topical ammonium lactate on cutaneous atrophy from a potent topical corticosteroid

Histórico: Os corticosteróides tópicos produzem alteraçöes atróficas na pele, inclusive diminuiçäo da espessura da epiderme e da substância essencial dérmica. Observamos que o lactato de amônio a 12 por cento produziu aumento da espessura da epiderme e aumento na qualidade de glicosaminoglicanos dérmicos. Objetivo: Determinar se o lactato de amônio a 12 por cento poderia minimizar a atrofia cutânea produzida por um corticosteróide tópico potente. Métodos: Ambos, o propionato de clobetasol e o lactato de amônio a 12 por cento, foram aplicados repetidas vezes sob patches oclusivos, bem como em patches abertos nos antebraços de voluntários durante 3 a 4 semanas. As amostras para biópsia foram avaliadas por análise de imagem quanto à espessura da epiderme e quanto à quantidade de glicosaminoglicanos dérmicos. Resultados: O lactato de amônio a 12 por cento atenuou significativamente a atrofia da epiderme e da derme sem nenhuma influência sobre a biodisponibilidade ou sobre as propriedades antiinflamatórias do corticosteróide. Conclusäo: O lactato de amônio a 12 por cento pode ser útil na atenuaçäo dos efeitos adversos do corticosteróide na pele

The effects of chemical disinfectants and sanitizers on Salmonella gallinarum

A atividade de diferentes compostos a base de iodo, amônia quaternária (QAC), fenol, glutaraldeido e cloro, contra Salmonella gallinarum foi avaliada na presença de matéria orgânica comumente encontrada em operaçöes avícolas. De um modo geral os compostos fenólicos apresentaram melhor desempenho, seguidos pelos produtos a base de amônia quaternária que, por sua vez, apresentaram melhor desempenho que os produtos a base de iodo. Todos apresentaram algum grau de inativaçäo quando utilizados na presença de raspa de madeira (maravalha), penugem, fezes de aves e raçäo para aves. A inativaçäo do produto químico foi mais profunda quando misturou-se, previamente, a bactéria na raçäo. Mesmo nestas condiçöes, o produto contendo glutaraldeído ainda manteve-se ativo. O composto contendo hipoclorito de sódio foi totalmente inibido pela presença de matéria orgânica