The integration of 3D printing into the pharmaceutical sciences opens new possibilities for personalized medicine. Poly(lactide) (PLA), a biodegradable and biocompatible polymer, is highly suitable for biomedical applications, particularly in the context of 3D printing. However, its processability often requires the addition of plasticizers. This study investigates the use of phase diagram modeling as a tool to guide the rational selection of plasticizers and to assess their impact on the thermodynamic and kinetic stability of PLA-based amorphous solid dispersions (ASDs) containing active pharmaceutical ingredients (APIs). Thermodynamic stability against API recrystallization was predicted based on the API solubility in PLA and Plasticizer-PLA carriers using the Conductor-like Screening Model for Real Solvents (COSMO-RS), while the kinetic stability of the ASDs was evaluated by modeling the glass transition temperatures of the mixtures. Two APIs, indomethacin (IND) and naproxen (NAP), with differing glass-forming abilities (i.e., recrystallization tendencies), and three plasticizers, triacetin (TA), triethyl citrate (TEC), and poly(L-lactide-co-caprolactone) (PLCL), were selected for investigation. The physical stability of ASD formulations containing 9 wt% API and plasticizer to PLA in two ratios, 10:81 and 20:71 w/w %, was monitored over time using differential scanning calorimetry and X-ray powder diffraction and compared with phase diagram predictions. All formulations were predicted to be thermodynamically unstable; however, those containing no plasticizer or with TEC and TA at 10 wt% were predicted to exhibit some degree of kinetic stability. Long-term physical studies corroborated these predictions. The correlation between the predicted phase behavior and long-term physical stability highlights the potential of phase diagram modeling as a tool for the rational design of ASDs in pharmaceutical 3D printing.

• MeSH
• Printing, Three-Dimensional * MeSH
• Citrates chemistry   MeSH
• Calorimetry, Differential Scanning methods   MeSH
• Chemistry, Pharmaceutical methods   MeSH
• Technology, Pharmaceutical methods   MeSH
• Indomethacin * chemistry   MeSH
• Crystallization MeSH
• Naproxen chemistry   MeSH
• Polyesters * chemistry   MeSH
• Solvents chemistry   MeSH
• Solubility * MeSH
• Drug Stability MeSH
• Thermodynamics MeSH
• Transition Temperature MeSH
• Triacetin chemistry   MeSH
• Plasticizers * chemistry   MeSH
• Publication type
• Journal Article MeSH

Autoři v článku prezentují epidemiologii, rizikové faktory přispívající ke vzniku urolitiáz, věnují se dále laboratornímu vyšetření u litiatiků, včetně problematiky analýzy složení konkrementů a jeho významu. Hlavním cílem článku je předložení metod neinvazivní léčby jednotlivých typů litiázy, především metafylaxe u pacientů s litiázou, a to jak režimových opatřeních, tak i užití farmak, které přispívají ke snížení četností recidiv litiázy, ale i komplikacím, které jsou s tímto onemocněním spojené.

The authors present the epidemiology, risk factors contributing to the development of urolithiasis, laboratory examination in lithiatic patients, including the analysis of the composition of concrements and its significance. The main goal of the article is to present the methods of non-invasive treatment of different types of lithiasis, especially metaphylaxis in patients with lithiasis, both regimen measures and the use of drugs that contribute to reducing the frequency of recurrences of lithiasis, as well as complications associated with this disease

• MeSH
• Allopurinol pharmacology   therapeutic use   MeSH
• Urinalysis methods   MeSH
• Cystinuria drug therapy   complications   MeSH
• X-Ray Diffraction methods   MeSH
• Diuretics pharmacology   therapeutic use   MeSH
• Durapatite therapeutic use   MeSH
• Hypercalciuria drug therapy   complications   MeSH
• Hyperoxaluria drug therapy   complications   MeSH
• Hyperuricemia drug therapy   complications   MeSH
• Urinary Tract Infections etiology   complications   MeSH
• Potassium Citrate pharmacology   therapeutic use   MeSH
• Calculi etiology   classification   therapy   MeSH
• Clinical Laboratory Techniques methods   MeSH
• Humans MeSH
• Oxalates adverse effects   MeSH
• Risk Factors MeSH
• Urolithiasis * diagnosis   drug therapy   prevention & control   MeSH
• Calcium, Dietary therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.

• MeSH
• Phosphates * chemistry   MeSH
• Histidine * chemistry   MeSH
• Hydrogen-Ion Concentration MeSH
• Citric Acid chemistry   MeSH
• Freeze Drying * methods   MeSH
• Magnetic Resonance Spectroscopy * methods   MeSH
• Buffers MeSH
• Spectrophotometry, Ultraviolet methods   MeSH
• Trehalose * chemistry   MeSH
• Publication type
• Journal Article MeSH

We explored the potential of a fungal strain Aspergillus costaricensis KS1 for modulating growth and nutrient mobilization in rice. At laboratory conditions, there was a decline in pH of the medium on inoculation with the strain and the production of citric acid was observed under broth conditions. Similarly, there was higher solubilization of tricalcium phosphate and siderophore production in liquid medium on inoculation with the strain. The effect of inoculation of KS1 was studied in rice and higher growth and yield were observed on inoculation compared to control. The content of phosphorus and iron in stem and roots of KS1 inoculated plants was higher in comparison with uninoculated control. There was also increased availability of phosphorus and iron content in soil grown with KS1 inoculated plants. In addition, inoculation with strain resulted in a higher content of volatile organic compounds such as linoleic acid, linolenic acid, and ethyl isoallocholate in stem of rice. A. costaricensis KS1 can be used for improving phosphorus and iron nutrition and impart tolerance against stresses in rice.

• MeSH
• Aspergillus * metabolism   growth & development   MeSH
• Phosphorus * metabolism   analysis   MeSH
• Calcium Phosphates metabolism   MeSH
• Hydrogen-Ion Concentration MeSH
• Plant Roots microbiology   metabolism   MeSH
• Citric Acid metabolism   MeSH
• Soil Microbiology MeSH
• Oryza * microbiology   metabolism   growth & development   MeSH
• Siderophores * metabolism   MeSH
• Plant Stems microbiology   metabolism   chemistry   MeSH
• Volatile Organic Compounds * metabolism   analysis   MeSH
• Iron * metabolism   MeSH
• Publication type
• Journal Article MeSH

Citrate buffers are commonly utilized in the field of biomolecule stabilization. We investigate their applicability in the frozen state within a range of initial pHs (2.5 to 8.0) and concentrations (0.02 to 0.60 M). Citrate buffer solutions subjected to various cooling and heating temperatures are examined in terms of the freezing-induced acidity changes, revealing that citrate buffers acidify upon cooling. The acidity is assessed with sulfonephthalein molecular probes frozen in the samples. Optical cryomicroscopy combined with differential scanning calorimetry was employed to investigate the causes of the observed acidity changes. The buffers partly crystallize and partly vitrify in the ice matrix; these processes influence the resulting pH and allow designing the optimal storage temperatures in the frozen state. The freezing-induced acidification apparently depends on the buffer concentration; at each pH, we suggest pertinent concentration, at which freezing causes minimal acidification.

• MeSH
• Citrates * MeSH
• Calorimetry, Differential Scanning MeSH
• Hydrogen-Ion Concentration MeSH
• Freeze Drying MeSH
• Buffers MeSH
• Freezing MeSH
• Publication type
• Journal Article MeSH

Průmyslové kultivace jsou klíčovým zdroje mnoha produktů. Každá kultivace má své vlastní produkční kmeny, podmínky a apara‐ tury. Nejčastěji používané jsou mechanicky míchané bioreaktory, díky jejich efektivní homogenizaci a všestrannosti. Přesto nejsou kompletně kompatibilní s organismy citlivými na střižné síly. Pro kultivaci takových organismů je vhodnější probublávaná kolona. Obecné porovnání probublávané kolony s míchaným bioreaktorem je náročné, jelikož je každá kultivace specifická. Probublávané kolony jsou jednoduché a snadno konstruovatelné bioreaktory, které vyžadují menší počáteční kapitál v porovnání s mechanicky míchaným bioreaktorem. Probublávané kolony nemají vnitřní komponenty a složité mechanické části a jsou proto méně náročné na údržbu. Nicméně, nejsou tak všestranné jako míchané bioreaktory a jsou mnohem více účelově používané. Přesto jsou v dnešním průmyslu nenahraditelné, především při velkoobjemových kultivacích mechanicky citlivých buněk, jako produkce kyseliny citrónové nebo antibiotik. Přímé porovnání probublávané kolony s mechanicky míchaným bioreaktorem je složité. Existují studie zaměřené na porovnání těch‐ to bioreaktorů při specifických kultivacích. Volba mezi těmito bioreaktory přesto závisí na dané aplikaci, buněčné linii a ekonomice celého procesu.

Industrial cultivations are a key source of many products. Each cultivation requires a specific producing organism, conditions and apparatus. Stirred tanks are most commonly used bioreactors, due to their efficient homogenization and versatility. However, they are not entirely suitable for cultivation of shear sensitive cells. Bubble columns are more suitable option for shear sensitive cells. Overall comparison of bubble columns and stirred tanks is complicated, since every cultivation is situational. Bubble columns are simple and easy to build bioreactors, which require a smaller starting investment compared to STRs. In the case of BCs without the internals, they required less maintenance due to lack of complex mechanical parts. However, BCs are not as ver‐ satile as STRs and are much more situational. Even though, they are unreplaceable part of today’s industry, especially in cultivations of shear sensitive cells in high volumes, like production of citric acid or antibiotics. Direct comparison of BC and STR is difficult. Some studies have conducted tests with specific cultivations on minds. Still, the final choice between these bioreactors depends on application, cell line used and final economics of the entire process.

• MeSH
• Anti-Bacterial Agents chemical synthesis   MeSH
• Biofuels MeSH
• Bioreactors * microbiology   MeSH
• Culture Techniques * methods   MeSH
• Citric Acid chemical synthesis   MeSH

Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts.

• MeSH
• Amino Acids metabolism   MeSH
• Citrates metabolism   MeSH
• Desmin * genetics   metabolism   MeSH
• Glucose metabolism   MeSH
• Hexokinase * genetics   metabolism   MeSH
• Cardiomyopathies * genetics   metabolism   MeSH
• Creatine Kinase, Mitochondrial Form metabolism   MeSH
• Fatty Acids metabolism   MeSH
• Myocardium metabolism   MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Oxidative Phosphorylation MeSH
• Glucose Transporter Type 1 metabolism   MeSH
• Proteomics MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Recommendations on the optimal preservation of 24 h urine for the metabolic work-up in urolithiasis patients are very heterogeneous. In case two such tests with different storage condition recommendations are being analysed, multiple collections would be needed, challenging especially elderly and very young patients. We therefore aimed to evaluate the stability of urine constituents under different storage conditions. MATERIAL AND METHODS: We collected urine samples from ten healthy volunteers and prepared aliquots to be stored either at room temperature or 4 °C. Some aliquots were preserved using hydrochloric acid prior to storage, some thereafter, some using the BD Urine preservation tube and some were not preserved at all. Storage duration was 0, 24, 48 or 72 h. In all samples calcium, magnesium, phosphorus, creatinine, oxalate, citrate and uric acid were measured and compared to the according reference sample. RESULTS: We could not find any significant deviation for any of the analytes and preanalytical treatment conditions compared to the associated reference sample. CONCLUSION: Preservation of 24 h urine for the metabolic evaluation in stone formers might not be necessary for sample storage up to 72 h.

• MeSH
• Magnesium MeSH
• Hydrogen-Ion Concentration MeSH
• Citric Acid MeSH
• Humans MeSH
• Risk Factors MeSH
• Aged MeSH
• Urolithiasis * diagnosis   urine   MeSH
• Calcium MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

PURPOSE: The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. METHODS: 216 women aged 25-60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. RESULTS: Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly (p < 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. CONCLUSION: SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. TRIAL REGISTRATION NUMBER: ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040 ; retrospectively registered.

• MeSH
• Ki-67 Antigen drug effects   MeSH
• Antioxidants administration & dosage   MeSH
• Administration, Intravaginal MeSH
• Cytodiagnosis MeSH
• Adult MeSH
• Uterine Cervical Dysplasia pathology   therapy   MeSH
• Genes, p16 MeSH
• Papillomavirus Infections therapy   virology   MeSH
• Cyclin-Dependent Kinase Inhibitor p16 drug effects   MeSH
• Colposcopy MeSH
• Citric Acid administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor analysis   MeSH
• Uterine Cervical Neoplasms prevention & control   MeSH
• Silicon Dioxide administration & dosage   MeSH
• Sodium Selenite administration & dosage   MeSH
• Pregnancy MeSH
• Vaginal Creams, Foams, and Jellies * MeSH
• Vaginal Smears MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

BACKROUND: The study aim was to establish if substitution of citrate with rt-PA for catheter lock once weekly can reduce the incidence of catheter-related blood stream infections (CR-BSI) or improve patency of tunneled haemodialysis catheters. METHODS: All incident patients undergoing insertion of a tunneled haemodialysis catheter were screened and included except those suffering infection or using oral anticoagulation. Study participants were randomized into two arms according to the solution applied as catheter lock: receiving either trisodium citrate (Citra-LockTM 4%) only or rt-PA (Actilyse® 1 mg/ml) on the middle session each week with citrate used on the first and third sessions. The incidence of CR-BSI (confirmed by positive blood culture), catheter non-function (complete obstruction), and malfunction (blood flow < 250 ml/min) was recorded. Statistical significance was tested with ANOVA, post hoc analysis was performed by means of multiple linear regression. RESULTS: Totally, 18 patients were included and followed during 655 haemodialysis sessions. No episode of CR-BSI was detected while 6 catheter non-functions (0.9% sessions) and 101 malfunctions (15.4% sessions) were recorded. The incidence of both events was equal between the study arms: 4 non-functions and 55 malfunctions in the rt-PA arm and 2 non-functions and 46 malfunctions in the citrate arm (p = 0.47 and p = 0.24, respectively). Additionally, the mean blood flow achieved did not differ significantly between the arms: 326 ± 1,8 and 326 ± 1,9 ml/min (p = 0.95) in rt-PA and citrate arms, respectively. Post hoc analysis identified time elapsed since previous session (β = 0.12, p = 0.005) and malfunction on previous session (β = 0.25, p < 0.001) as significant factors affecting the occurrence of malfunction. By contrast, the study arm, rt-PA application on previous session, and catheter vintage did not enter the model. CONCLUSION: Substitution of citrate with rt-PA for catheter lock does not reduce the incidence of catheter malfunction neither does it affect the blood flow achieved during haemodialysis. Catheter patency is related rather to the time interval between sessions and to previous malfunction (thus probably reflecting undefined individual factors). The incidence of CR-BSI within pre-selected haemodialysis population is sporadic (less than 1 per 4.3 patient years in our sample). TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12612000152820 . Retrospectively registered 03/02/2012.

• MeSH
• Central Venous Catheters * MeSH
• Citrates therapeutic use   MeSH
• Renal Dialysis instrumentation   MeSH
• Double-Blind Method MeSH
• Fibrinolytic Agents therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Drug Substitution MeSH
• Prospective Studies MeSH
• Vascular Patency MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Tissue Plasminogen Activator therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH