Brilacidin, a novel antifungal agent against Cryptococcus neoformans.

Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

Five-year follow-up of a phase I trial of donor-derived modified immune cell infusion in kidney transplantation.

Background: The administration of modified immune cells (MIC) before kidney transplantation led to specific immunosuppression against the allogeneic donor and a significant increase in regulatory B lymphocytes. We wondered how this approach affected the continued clinical course of these patients. Methods: Ten patients from a phase I clinical trial who had received MIC infusions prior to kidney transplantation were retrospectively compared to 15 matched standard-risk recipients. Follow-up was until year five after surgery. Results: The 10 MIC patients had an excellent clinical course with stable kidney graft function, no donor-specific human leukocyte antigen antibodies (DSA) or acute rejections, and no opportunistic infections. In comparison, a retrospectively matched control group receiving standard immunosuppressive therapy had a higher frequency of DSA (log rank P = 0.046) and more opportunistic infections (log rank P = 0.033). Importantly, MIC patients, and in particular the four patients who had received the highest cell number 7 days before surgery and received low immunosuppression during follow-up, continued to show a lack of anti-donor T lymphocyte reactivity in vitro and high CD19+CD24hiCD38hi transitional and CD19+CD24hiCD27+ memory B lymphocytes until year five after surgery. Conclusions: MIC infusions together with reduced conventional immunosuppression were associated with good graft function during five years of follow-up, no de novo DSA development and no opportunistic infections. In the future, MIC infusions might contribute to graft protection while reducing the side effects of immunosuppressive therapy. However, this approach needs further validation in direct comparison with prospective controls. Trial registration: https://clinicaltrials.gov/, identifier NCT02560220 (for the TOL-1 Study). EudraCT Number: 2014-002086-30.

Edge magnetization and thermally induced spin current in nanostructured graphene.

In this work, the magnetic states and thermally induced spin currents in graphene nanoflake sizes with different sizes and shapes have been investigated using Hubbard model combined with non-equilibrium Green's function method. In addition to the antiferromagnetic (AFM) state governed by the sizes, shapes, armchair bond densities, and Coulomb energy, our calculations have also pointed out the emergence of ferromagnetic (FM) and complex magnetic states when the gate voltage is invoked in the graphene nanoflakes. More prominently, by exploiting the geometric symmetry of the nanoflakes without external fields, a pure spin current and zero charge current are generated in spin caloritronic device when the graphene nanoflakes are both in the AFM and FM states. The formation of pure spin currents driven by temperature difference depends on the graphene nanoflakes' size, shape, temperature and gate voltage as well. The study also shows the outstanding advantages of diamond-shaped graphene nanoflakes in both magnetic properties and spin currents. This result paves the way for the possibility of practical applications of graphene materials in spintronics and spin caloritronics.

Appropriate Antibiotic Use and Associated Factors in Vietnamese Outpatients.

Background: Inappropriate antibiotic use among outpatients is recognized as the primary driver of antibiotic resistance. A proper understanding of appropriate antibiotic usage and associated factors helps to determine and limit inappropriateness. We aimed to identify the rate of appropriate use of antibiotics and identify factors associated with the inappropriate prescriptions. Methods: We conducted a cross-sectional descriptive study in outpatient antibiotic use at a hospital in Can Tho City, Vietnam, from August 1, 2019, to January 31, 2020. Data were extracted from all outpatient prescriptions at the Medical Examination Department and analyzed by SPSS 18 and Chi-squared tests, with 95% confidence intervals. The rationale for antibiotic use was evaluated through antibiotic selection, dose, dosing frequency, dosing time, interactions between antibiotics and other drugs, and general appropriate usage. Results: A total of 420 prescriptions were 51.7% for females, 61.7% with health insurance, and 44.0% for patients with one comorbid condition. The general appropriate antibiotic usage rate was 86.7%. Prescriptions showed that 11.0% and 9.5% had a higher dosing frequency and dose than recommended, respectively; 10.2% had an inappropriate dosing time; 3.1% had drug interactions; and only 1.7% had been prescribed inappropriate antibiotics. The risk of inappropriate antibiotic use increased in patients with comorbidities and antibiotic treatment lasting >7 days (p < 0.05). Conclusions: The study indicated a need for more consideration when prescribing antibiotics to patients with comorbidities or using more than 7 days of treatment.

Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption.

Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.

Correction to: an automatic water detection approach using Landsat 8 OLI and Google earth engine cloud computing to map lakes and reservoirs in New Zealand.

In the published article:"An automatic water detection approach using Landsat 8 OLI and Google Earth Engine cloud computing to map lakes and reservoirs in New Zealand", the Acknowledgements was published incorrectly and funding statement was missing.

An automatic water detection approach using Landsat 8 OLI and Google Earth Engine cloud computing to map lakes and reservoirs in New Zealand.

Monitoring water surface dynamics is essential for the management of lakes and reservoirs, especially those are intensively impacted by human exploitation and climatic variation. Although modern satellites have provided a superior solution over traditional methods in monitoring water surfaces, manually downloading and processing imagery associated with large study areas or long-time scales are time-consuming. The Google Earth Engine (GEE) platform provides a promising solution for this type of "big data" problems when it is combined with the automatic water extraction index (AWEI) to delineate multi-temporal water pixels from other forms of land use/land cover. The aim of this study is to assess the performance of a completely automatic water extraction framework by combining AWEI, GEE, and Landsat 8 OLI data over the period 2014-2018 in the case study of New Zealand. The overall accuracy (OA) of 0.85 proved the good performance of this combination. Therefore, the framework developed in this research can be used for lake and reservoir monitoring and assessment in the future. We also found that despite the temporal variability of climate during the period 2014-2018, the spatial areas of most of the lakes (3840) in the country remained the same at around 3742 km2. Image fusion or aerial photos can be employed to check the areal variation of the lakes at a finer scale.

The possible critical role of T-cell help in DSA-mediated graft loss.

In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect. Patients positive for both pretransplant DSA and sCD30 appear to require special measures, such as the elimination of DSA from the circulation, potent immunosuppression, good HLA-matching, and intense post-transplant monitoring, whereas exclusion of DSA-positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement-activating.

Neuroplasticity-based auditory training via laptop computer improves cognition in young individuals with recent onset schizophrenia.

OBJECTIVE: Cognitive deficits that characterize schizophrenia are present in the prodrome, worsen with illness onset, and predict functional outcome. Cognitive dysfunction is thus a critical target for early intervention in young individuals with recent onset schizophrenia. METHOD: This 2-site double-blind randomized controlled trial investigated cognitive training of auditory processing/verbal learning in 86 subjects with recent onset schizophrenia (mean age of 21 years). Subjects were given laptop computers to take home and were asked to perform 40 hours of training or 40 hours of commercial computer games over 8 weeks. We examined cognitive measures recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS), symptoms, and functioning. We also assessed baseline reward anticipation to index motivational system functioning and measured changes in auditory processing speed after 20 hours of training to assess target engagement. RESULTS: Auditory training subjects demonstrated significant improvements in global cognition, verbal memory, and problem solving compared with those of computer games control subjects. Both groups showed a slight but significant decrease in symptoms and no change in functional outcome measures. Training-induced cognitive gains at posttraining showed significant associations with reward anticipation at baseline and with improvement in auditory processing speed at 20 hours. CONCLUSION: Neuroscience-informed cognitive training via laptop computer represents a promising treatment approach for cognitive dysfunction in early schizophrenia. An individual's baseline motivational system functioning (reward anticipation), and ability to engage in auditory processing speed improvement, may represent important predictors of treatment outcome. Future studies must investigate whether cognitive training improves functioning and how best to integrate it into critical psychosocial interventions.

Health services for reproductive tract infections among female migrant workers in industrial zones in Ha Noi, Viet Nam: an in-depth assessment.

BACKGROUND: Rural-to-urban migration involves a high proportion of females because job opportunities for female migrants have increased in urban industrial areas. Those who migrate may be healthier than those staying in the village and they may benefit from better health care services at destination, but the 'healthy' effect can be reversed at destination due to migration-related health risk factors. The study aimed to explore the need for health care services for reproductive tract infections (RTIs) among female migrants working in the Sai Dong industrial zone as well as their services utilization. METHODS: The cross sectional study employed a mixed method approach. A cohort of 300 female migrants was interviewed to collect quantitative data. Two focus groups and 20 in-depth interviews were conducted to collect qualitative data. We have used frequency and cross-tabulation techniques to analyze the quantitative data and the qualitative data was used to triangulate and to provide more in-depth information. RESULTS: The needs for health care services for RTI were high as 25% of participants had RTI syndromes. Only 21.6% of female migrants having RTI syndromes ever seek helps for health care services. Barriers preventing migrants to access services were traditional values, long working hours, lack of information, and high cost of services. Employers had limited interests in reproductive health of female migrants, and there was ineffective collaboration between the local health system and enterprises. These barriers were partly caused by lack of health promotion programs suitable for migrants. Most respondents needed more information on RTIs and preferred to receive these from their employers since they commonly work shifts--and spend most of their day time at work. CONCLUSION: While RTIs are a common health problem among female migrant workers in industrial zones, female migrants had many obstacles in accessing RTI care services. The findings from this study will help to design intervention models for RTI among this vulnerable group such as communication for behavioural impact of RTI health care, fostered collaboration between local health care services and employer enterprises, and on-site service (e.g. local or enterprise health clinics) strengthening.

Effects of Lactobacillus rhamnosus GG on saliva-derived microcosms.

OBJECTIVE: The probiotic strain Lactobacillus rhamnosus GG (LGG) is shown to hamper the presence of mutans streptococci in saliva and may have positive effects on oral health. We investigated the effects of LGG on the cariogenic potential and microbial composition of saliva-derived microcosms. DESIGN: Single and dual species biofilms of LGG and Streptococcus mutans, and saliva-derived microcosms with or without LGG were grown in an Active Attachment Biofilm model. The microcosms were grown on bovine dentin/enamel discs in the presence or absence of sucrose (suc+/suc-). The presence of LGG was determined by multiplex ligation-dependent probe amplification (MLPA) and real-time PCR. Mutans streptococci (MS) and total viable counts, pH of the spent medium, capacity of lactate formation and integrated mineral loss in dentin was assessed. MLPA was used for identification and relative quantification of 20 oral microorganisms in the microcosms. Principal Component Analysis was applied to MLPA data. RESULTS: LGG inhibited the growth of S. mutans in dual species biofilms and did not affect the pH. LGG established in saliva-derived microcosms and reduced MS counts significantly, but did not affect pH or dentin demineralization. Simultaneous growth of the microcosms with LGG under heavy cariogenic conditions (suc+) introduced a compositional shift in the microbial community. The CFU, real-time PCR and MLPA data correlated significantly. CONCLUSION: We conclude that LGG established into and inhibited the growth of MS in complex saliva-derived biofilms, but this had no significant effect on cariogenic potential of the microcosms. This suggests that other microorganisms besides MS were responsible for increased cariogenicity of sucrose-exposed biofilms.

Effects of probiotic Lactobacillus salivarius W24 on the compositional stability of oral microbial communities.

Probiotics are microorganisms beneficial to gastrointestinal health. Although some strains are also known to possess positive effects on oral health, the effects of most intestinal probiotics on the oral microflora remain unknown. We assessed the ability of the intestinal probiotic Lactobacillus salivarius W24 to incorporate into and to affect the compositional stability and cariogenicity of oral microbial communities. Microtiter plates with hydroxyapatite discs were incubated with W24 ("+W24") or without W24 ("-W24") and saliva from four individuals in plain ("-sucrose") or sucrose-supplemented ("+sucrose") medium. Biofilms were subjected to community profiling by 16S rRNA gene-based Denaturing Gradient Gel Electrophoresis (DGGE) after 72h growth. Diversity (Shannon-Weaver index) and similarities (Pearson correlation) between biofilm communities were calculated. Microcosms "+sucrose" were less diverse and more acidic than "-sucrose" microcosms (p<0.001). The effects of W24 on the community profiles were pH dependent: at pH 4 ("+sucrose"), the respective "+W24" and "-W24" microcosms differed significantly more from each other than if the pH was approximately 7 ("-sucrose"). The pH of "+W24/+sucrose" microcosms was lower (p<0.05) than the pH of the microcosms supplemented with sucrose alone ("-W24/+sucrose"). Although not able to form a monospecies biofilm, L. salivarius W24 established itself into the oral community if inoculated simultaneously with the microcosm. In the presence of sucrose and low pH, W24 further lowered the pH and changed the community profiles of these microcosms. Screening of probiotics for their effects on oral microbial communities allows selecting strains without a potential for oral health hazards.

Crusted Norwegian scabies in an adult with Langerhans cell histiocytosis: mishaps leading to systemic chemotherapy.

BACKGROUND: Crusted Norwegian scabies is a rare hyperkeratotic variant of scabies infestation. We report herein a case of crusted scabies in a woman with underlying Langerhans cell histiocytosis (LCH). OBSERVATIONS: A 49-year-old woman with LCH was hospitalized owing to marked thrombocytopenia. Her hyperkeratotic skin eruption was thought to be secondary to LCH because several years earlier, she had positive biopsy findings and had been diagnosed as having LCH. After a 1-month hospital stay, her laboratory values improved despite worsening of her skin lesions. CONCLUSION: Analysis of skin scrapings confirmed the presence of scabies, and resolution was achieved with a 1-dose ivermectin treatment.

Physical and Chemical Stability of Treprostinil Sodium Injection Packaged in Plastic Syringe pump Reservoirs.

The objective of this study was to evaluate the physical and chemical stability of treprostinil (as sodium) injections in concentrations of 1, 2.5, 5 and 10 mg/mL packaged in MiniMed plastic syringe pump reservoirs. Test samples of treprostinil (as sodium) injections having concentrations of 1, 2.5, 5, and 10 mg/mL were packaged as 3 mL of drug solution in 3-mL MiniMed plastic syringe pump reservoirs, sealed with plastic tip caps and stored at -20 deg C, 4 deg C, 23 deg C and 37 deg C for 60 days. Evaluations for physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed using visual observation in normal room light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated by using a stability-indicating high-performance liquid chromatographic analytical technique. All samples of treprostinil (as sodium) injection remained free of visible precipitation throughout the study. Little or no change in haze level and in particulates of greater than or equal to 10 micrometers was found. Changes in treprostinil concentration were found to be small; treprostinil sodium concentrations were found to be 95% or greater over 60 days at all temperatures studied. Treprostinil (as sodium) injections at concentrations ranging from 1 to 10 mg/mL can be packaged in MiniMed plastic syringe reservoirs, stored and shipped with little or no loss of drug stability.

Physical and Chemical Stability of Morphine Sulfate 5mg/mL and 50mg/mL Packaged in Plastic Syringes.

The objective of this study was to evaluate the physical and chemical stability of morphine sulfate in concentrations of 5 mg/mL in 0.9% sodium chloride injection and 50 mg/mL in both 0.9% sodium chloride injection and in sterile water for injection packaged in plastic syringes. Test samples of morphine sulfate 5-mg/mL and 50-mg/mL solutions were packaged as 20 mL of drug solution in 30-mL plastic syringes, sealed with plastic tip caps, and stored at 4 deg C and 23 deg C for 60 days. Test samples were also stored at -20 deg C and 37 deg C (temperature extremes that might be encountered during shipping) for 2 days. Evaluations of physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed by means of visual observation in normal room light as well as with a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stabililty of the drug was evaluated by using a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique. All samples of morphine sulfate 5-mg/mL solutions stored at 4 deg C, 23 deg C, and 37 deg C and the 50-mg/mL solutions stored at 23 deg C and 37 deg C remained free of precipitation throughout the study. In those solutions, little or no change in measured particulate burden or haze level was found, However, the solutions of morphine sulfate 50 mg/mL in 0.9% sodium chloride injection and in sterile water for injection exhibited an obvious precipitate within 2 to 4 days of storage at 4 deg C. Warming the solution to redissolve the visible precipitate left a substantial microparticulate content of up to 29,000 microparticulates/mL. When both morphine sulfate concentrations were frozen, precipitation was also noted. Upon thawing, the solutions yielded substantial measured microparticulate quantities of more than 20,000 microparticulates/mL in the 5-mg/mL concentration and more than 52,000 microparticulates/mL in the 50 mg/mL concentration. In addition, morphine sulfate 50mg/mL in both diluents exhibited a slight yellow discoloration after 30 days of storage at 23 deg C. Little or no loss of morphine sulfate occurred in any of the samples at any storage temperature throughout the study. Analysis of the samples after redissolving the visible precipitate in the low-temperature samples demonstrated that the morphine sulfate remained intact. Morphine concentrations were found to be 95% or greater over 60 days when stored at both 4 deg C and 23 deg C. In addition, morphine concentrations were greater than 97% when stored at -20 deg C, and they were 98% or greater when stored at 37 deg C after 2 days. However. exposure to low temperatures may result in precipitation, including microparticulate content that does not fully redissolve upon warming.

Physical and chemical stability of low and high concentrations of morphine sulfate with clonidine hydrochloride packaged in plastic syringes.

The objective of this study was to evaluate the physical and chemical stability of morphine sulfate 5 mg/mL with clonidine hydrochloride 0.25 mg/mL in 0.9% sodium chloride injection and morphine sulfate 50 mg/mL with clonidine hydrochloride 4 mg/mL in sterile water for injection when packaged in plastic syringes. Test samples of morphine sulfate 5-mg/mL with clonidine hydrochloride 0.25-mg/mL and morphine sulfate 50-mg/mL with clonidine hydrochloride 4-mg/mL solutions were packaged as 20 mL of drug solution in 30-mL plastic syringes, sealed with plastic tip caps, and stored at 4 deg C and 23 deg C for 60 days. Test samples were also stored at -20 deg C and 37 deg C (temperature extremes that might be encountered during shiping) for 2 days. Evaluations for physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed by means of visual observation in normal room light and with a high-intensity monodirectional light beam. In addition turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated by means of a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique. All samples of morphine sulfate 5-mg/mL with clonidine hydrochloride 0.25mg/mL solutions stored at 4 deg C, 23 deg C, and 37 deg C and the morphine sulfate 50-mg/mL with clonidine HCl 4-mg/mL solrtions stored at 23 deg C and 37 deg C remained free of precipitation throughout the study. Little or no change in measured particulate burden and haze level were found in those solutions. However, morphine sulfate 50 mg/ml with clonidine HCl 4 mg/mL stored at 4 deg C exhibited an obvious precipitate within 2 to 4 days. Warming the solution to redissolve the precipitate left a substantial microparticulate content that was measured to be more than 33,000 microparticulates/mL. Upon freezing, both high- and low- concentration samples precipitated and yielded substantial measured microparticulate quantities up to 35,000 microparticulates/mL in the low-concentration combination and 50,000 microparticulates/mL in the high-concentration combination. In addition, as with morphine sulfate 50 mg/mL alone, the high-concentration combination exhibited a slight yellow discoloration after 30 days of storage at 23 deg C. Little or no loss of morphine sulfate and clonidine hydrochloride occurred in any of the samples at any storage temperature throughout the study. Morphine concentrations were found to be about 98% or greater, and clonidine hydrochloride concentrations were about 97% or greater throughout the study period under each storage condition. Morphine sulfate solutions at concentrations ranging from 5 to 50 mg/mL combined with clonidine hydrochloride ranging from 0.25 to 4 mg/mL can be packaged in plastic syringes, stored and shipped with little or no loss of drug. However, freezing should be avoided.

Physical and chemical stability of low and high concentrations of morphine sulfate with bupivacaine hydrochloride packaged in plastic syringes.

The objective of this study was to evaluate the physical and chemical stability of morphine sulfate 5 mg/mL with bupivacaine hydrochloride 2.5 mg/mL in 0.9% sodium chloride injection and morphine sulfate 50 mg/mL with bupivacaine hydrochloride 25 mg/mL in sterile water for injection packaged in plastic syringes. Test samples of morphine sulfate 5-mg/mL with bupicvacaine hydrochloride 2.5-mg/mL and morphine sulfate 50-mg/mL with bupivacaine hydrochloride 25-mg/mL solutions were packaged as 20 mL of drug solution in 30-mL plastic syringes, sealed with plastic tip caps, and stored at 4 deg C and 23 deg C for 60 days. Test samples were also stored at -20 deg C and 37 deg C (temperature extremes that might be encountered during shipping) for 2 days. Evaluations for physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed by means of visual observation under normal room light and with a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated with a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique. All test samples remained free of visible precipitation throughout the study. The inclusion of the bupivacaine hydrochloride prevented the precipitation of morphine sulfate that occurs at a lower storage temperature. For solutions stored at 4 deg C, 23 deg C, and 37 deg C, little or no change in measured particulate burden and haze level were found. However, samples stored frozen at -20 deg C exhibited a substantial microparticulate content upon thawing that was measured to be nearly 12,000 microparticulates/mL. Most samples were clear and colorless throughout the study. However, morphine sulfate 50 mg/mL exhibited a slight yellow discoloration after 7 days of storage at 23 deg C. Little or no loss of morphine sulfate and bupivacaine hydrochloride occurred in any of the samples at any storage temperature throughout the study. Morphine concentrations were found to be about 97% or greater, and bupivacaine hydrochloride concentrations were about 95% or greater throughout the study period under each storage condition. Morphine sulfate solutions at concentrations ranging from 5 mg/mL to 50 mg/mL combined with bupivacaine hydrochloride 2.5 mg/mL to 25 mg/mL can be packaged in plastic syringes stored, and shipped with little or no loss of drug. However, freezing should be avoided.

Physical and Chemical Stability of Hydromorphone Hydrochloride 1.5 and 80 mg/mL Packaged in Plastic Syringes.

The objective of this study was to evaluate the physical and chemical stability of hydromorphone hydrochloride in concentrations of 1.5 and 80 mg/mL in 0.9% sodium chloride injection packaged in plastic syringes. Test samples of hydromorphone hydrochloride 1.5- and 80-mg/mL solutions were packaged as 20 mL of drug solution in 30-mL plastic syringes, sealed with plastic tip caps, and stored at 4 deg C and 23 deg C for 60 days and at -20 deg C and 37 deg C (temperature extremes that might be encounterd during shipping) for 2 days. Evaluations for physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed by means of visual observation in normal room light with a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. The chemical stability of the drug was evaluated by means of a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique. All samples of hydromorphone hydrochloride remained free of visible precipitation throughout the study. Those solutions stored at 4 deg C, 23 deg C, or 37 deg C exhibited little or no change in measured particulate burden and haze level. Freezing the solution resulted in an increase in microparticulate content that did not redissolve when the solution was warmed at room temperature. Little or no loss of hydromorphone hydrochloride occurred in any of the samples at any storage temperature throughout the study. Hydromorphone hydrochloride concentrations were found to be 95% or greater over 60 days at both 4 deg C and 23 deg C; concentrations were greater than 97% at both -20 deg C and 37 deg C after 2 days. Hydromorphone hydrochloride solutions at concentrations ranging from 1.5 to 80 mg/mL in 0.9% sodium chloride injection can be packaged in plastic syringes, stored, and shipped with little or no loss of drug. Freezing should be avoided.