Exploring the needs and coping strategies of family caregivers taking care of dying patients at home: a field study.

BACKGROUND: Most Chinese patients chose to die at home, therefore there is a reliance on the family caregivers to be involved in their palliative care. The needs and coping strategies of family caregivers in home-based palliative care are rooted in culture. Little is known about the needs and coping strategies of family caregivers taking care of dying patients at home. METHODS: A field study using semi-structured interview, participant observation, documents and records collection was employed. The study was conducted in two palliative care outpatient departments in tertiary hospitals and four communities in Beijing, China from March 2021 to July 2022. Using purposive sampling, twenty-five family caregivers were recruited. All collected data were analyzed using content analysis approach. RESULTS: Five themes emerged, including three care needs and two coping strategies. Family caregivers need to learn care skills and acquire care resources, including (i) decision-making about home-based palliative care, (ii) improving patient's quality of life, and (iii) signs of final hours and funeral procedures. In facing the care burden, family caregivers coped by (iv) balancing the roles of caregivers and individuals: giving priority to patient care while maintaining their own normal life. In facing the death of a loved one, family caregivers responded by (v) making room for coming death by facing death indirectly and "rescuing" patients for consolation while preparing for the coming death. CONCLUSION: Family caregivers strive to balance the roles of being caregivers and being themselves. As caregivers, they actively prepare patients for good death with no regrets. As individuals, they preserve themselves from being hurt to maintain normal life. The needs of family caregivers focus on caregiver role and are manifested in care skills and resources. TRIAL REGISTRATION: Not registered.

SET-CAN/NUP214 fusion gene in leukemia: general features and clinical advances.

SET-CAN/NUP214 fusion is a recurrent event commonly observed in adult male patients diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and has occasionally been reported in other diseases such as acute myeloid leukemia (AML), myeloid sarcoma (MS), acute undifferentiated leukemia (AUL), chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL). This fusion gene is derived from chromosome del(9)(q34.11;q34.13) or t(9;9)(q34;q34) and may have an inhibitory effect on primitive progenitor differentiation. The prognosis of the reported patients is varied, with these patients often show resistance to chemotherapy regimens that include high doses of glucocorticoids. The optional treatment has not been determined, more cases need to be accumulated and evaluated. The scope of this review is to summarize the general features and prognostic significance in leukemia associated with the SET-CAN/NUP214 fusion gene and to discuss the methods of detection and treatment, aiming at providing some useful references for relevant researchers in the field of blood tumor.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

Human umbilical cord mesenchymal stem cells ameliorate erectile dysfunction in rats with diabetes mellitus through the attenuation of ferroptosis.

BACKGROUND: Erectile dysfunction (ED), as one of the most prevalent consequences in male diabetic patients, has a serious impact on men's physical and mental health, and the treatment effect of diabetic mellitus erectile dysfunction (DMED) is often worse. Therefore, the development of a novel therapeutic approach is urgent. As stem cells with high differentiation potential, human umbilical cord mesenchymal stem cells (HUCMSCs) have been widely used in the treatment of diseases in other systems, and are expected to be a promising strategy for the treatment of DMED. In this study, we investigated the role of HUCMSCs in managing erectile function in rat models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and compared the effects of two different injection methods. METHODS: T1DM and T2DM ED rats were given labelled HUCMSCs by corpus cavernosum injection and tail vein injection, respectively. ICP and MAP were monitored simultaneously by electrical stimulation four weeks after injection to indicate the erectile function of rats. To track the development and colonisation capabilities of stem cells, we performed EdU assay with penile tissue. The histological changes of the penis were observed by hematoxylin-eosin staining, and Masson's trichrome staining was conducted to evaluate the smooth muscle content and the degree of fibrosis in the rat penis. Then, we employed specific kits to measure the level of NO, cGMP, MDA, SOD and Fe in penis. Electron transmission microscopy was implemented to observe morphology of mitochondria. Besides, western blot and immunofluorescence staining were performed to demonstrate the expression of ferroptosis-related genes. RESULTS: We found that HUCMSCs improved erectile function in T1DM and T2DM ED rats, with no difference in efficacy between corpus cavernosum injection and tail vein injection. The EdU assay revealed that only a tiny percentage of HUCMSCs colonised the corpus cavernosum, while smooth muscle in the penis expanded and collagen decreased following HUCMSC injection. Moreover, the levels of oxidative stress in the penis of the rats given HUCMSCs were dramatically reduced, as was the tissue iron content. HUCMSCs normalised mitochondrial morphology within corpus cavernosum smooth muscle cells (CCSMCs), which were characteristically altered by high glucose. Furthermore, the expression of ferroptosis inhibitory genes SLC7A11 and GPX4 was obviously elevated in CCSMCs after stem cell management, but the abundances of ACSL4, LPCAT3 and ALOX15 showed the polar opposite tendency. CONCLUSIONS: HUCMSCs can effectively and safely alleviate erectile dysfunction in T1DM and T2DM ED rats, while restoring erectile function by attenuating diabetes-induced ferroptosis in CCSMCs. Additionally, this study provides significant evidence for the development of HUCMSCs as a viable therapeutic strategy for DMED.

Acetyl-L-carnitine improves erectile function in bilateral cavernous nerve injury rats via promoting cavernous nerve regeneration.

BACKGROUND: Neurogenic erectile dysfunction (NED) caused by cavernous nerve (CN) injury is a typical complication after pelvic surgery, which lacks efficient treatments. Acetyl-L-carnitine (ALCAR) has been proven to promote nerve repair. OBJECTIVES: To investigate the effect and potential mechanism of ALCAR in the treatment of NED. MATERIALS AND METHODS: Thirty-two rats were randomly divided into bilateral CN injury (BCNI) group, BCNI + lower-dose ALCAR (50 mg/kg/day) group, BCNI + higher-dose (100 mg/kg/day) group, and sham-operated group. Erectile function was assessed 14 days after daily intraperitoneal injection of ALCAR or placebo. The penile tissues were gathered for subsequent histological and molecular biological analysis. Rat Schwann cell (SC) line S16 was used to verify the mechanism of ALCAR in vitro. RESULTS: We found that the erectile function of the rats in the BCNI group was severely impaired, which was improved considerably in both BCNI+ALCAR-LD and BCNI+ALCAR-HD groups. Also, we observed decreased smooth muscle and increased collagen content in the corpus cavernosum in the BCNI group. The expressions of fibrosis markers transforming growth factor-beta (TGF-ß), connective tissue growth factor (CTGF), and Smad 2/3 were significantly up-regulated in the BCNI group. The above changes were alleviated after the administration of lower and higher-dose ALCAR. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate pathway (cGMP) was promoted and the Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway was inhibited in the corpus cavernosum of BCNI rats after ALCAR treatment, accompanied by increased neuronal nitric oxide synthase (nNOS) and down-regulated tyrosine hydroxylase (TH). In vitro, ALCAR promoted the migration and proliferation of SC and increased the expression of 22-kD peripheral myelin protein and nerve growth factor (NGF). Further, rats treated with ALCAR had high expression of ATF3 and S100 in the distal nerve tissues of the CN extrusion site. DISCUSSION AND CONCLUSION: ALCAR could promote nerve repair and regeneration, inhibit penile fibrosis, and improve penile erection by promoting the proliferation and migration of SC and the secretion of NGF. Our study confirms that ALCAR may be a potential treatment strategy for NED.

Correlation Between Severity of Illness and Levels of Free Triiodothyronine, Interleukin-6, and Interleukin-10 in Patients with Acute Pancreatitis.

BACKGROUND Acute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity. MATERIAL AND METHODS Enrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients. RESULTS In our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769-0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542-0.715]), our predictive model (AUC 0.918 [95% CIs 0.875-0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P<0.05). CONCLUSIONS The predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.

Negative pressure wound therapy for surgical site infections: A systematic review and meta-analysis.

OBJECTIVE: Negative pressure wound therapy is one of the most common treatments for infected wounds. The aim of this meta-analysis was to compare the efficacy of negative pressure wound therapy with conventional treatment methods in the treatment of surgical site infection. DESIGN: This study is registered with International Prospective Register of Systematic Reviews. DATA SOURCES: The Pubmed, Embase and the Cochrane Central Register of Controlled Trials databases were searched. METHODS: The systematic review was searched by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. All trials reporting the use of negative pressure wound therapy for surgical site infection treatment were included regardless of surgery type. The primary outcome measure was wound healing. Secondary outcomes were length of hospital stay, medical costs, adverse events, and reoperation rates. Results are presented with 95% confidence intervals and report estimates as odds ratios. Heterogeneity was determined through the I2 test, with I2  > 50% indicating substantial heterogeneity and p < .10 significance. The search was performed on 10 March 2020. RESULTS: We identified 13 eligible trial comparisons, of which 2 were randomized controlled trials and 11 cohort study. Negative pressure wound therapy in surgical site infection (SSI) patients significantly increased wound healing rate, accelerated wound healing time, increased daily wound healing area, reduced hospital stay, and reduced adverse events. However, negative pressure wound therapy was associated with increased medical costs. CONCLUSION: Negative pressure wound therapy may be more effective for the treatment of surgical site infection relative to conventional debridement, dressings and other treatments. However, further high-quality randomized controlled trials are needed to determine the most optimal application of negative pressure wound therapy. IMPACT: Negative pressure wound therapy is the best treatment strategy for surgical site infection. This study can improve medical practitioners' awareness of negative pressure wound therapy for surgical site infection, promoting the development of relevant randomized controlled trials.

[Mechanism of gasdermin D on intestinal injury in severe acute pancreatitis by mediating pyroptosis].

OBJECTIVE: To investigate the function of gasdermin D (GSDMD) in intestinal damage of mice with severe acute pancreatitis (SAP). METHODS: The healthy C57BL/6 mice were divided into four groups randomly, including normal saline (NS) group, small interfering RNA (siRNA)-NS group, SAP model group and siRNA-SAP group, with 6 mice in each group. The SAP mouse model was reproduced by intraperitoneal injection of caerulein 50 µg/kg combined with lipopolysaccharide (LPS) 10 mg/kg; the NS group was given the same amount of NS; in the siRNA-SAP group and siRNA-NS group, siRNA 50 mg/kg was injected through the tail vein three times before modeling or injection of NS. The blood of mice eyeball in each group was taken 12 hours after modeling, and serum interleukins (IL-1ß, IL-18) levels were detected by enzyme linked immunosorbent assay (ELISA). The mice were sacrificed to observe the general changes in abdominal cavity, the pancreas and ileum tissues were taken to observe the pathological changes under a light microscope. The expression of long-chain non-coding RNA uc.173 (lnc uc.173) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect the expression of tight junction proteins zonula occluden-1 (ZO-1) and Occludin in intestinal mucosal epithelial cells. Western blotting was used to detect the GSDMD protein expression level in the intestinal tissue. RESULTS: The serum levels of IL-1ß and IL-18 in the SAP model group were significantly higher than those in the NS group and the siRNA-NS group [IL-1ß (ng/L): 146.66±1.40 vs. 44.48±5.76, 81.49±10.75, IL-18 (ng/L): 950.47±177.09 vs. 115.43±16.40, 84.84±21.90, all P < 0.05]; and the levels of IL-1ß and IL-18 in the siRNA-SAP group were significantly lower than those in the SAP model group [IL-1ß (ng/L): 116.26±15.54 vs. 146.66±1.40, IL-18 (ng/L): 689.96±126.08 vs. 950.47±177.09, both P < 0.05]. General observation showed that there were no obvious abnormalities in the abdominal cavity of the mice in the NS and siRNA-NS groups; the mice in the SAP model group and the siRNA-SAP group had different degrees of edema and congestion in the intestine; compared with the SAP model group, the abnormalities in the siRNA-SAP group was significantly reduced. Under light microscope, there were no obvious changes in the pancreas and intestinal mucosa in the NS group and the siRNA-NS group; the pancreatic tissue of the SAP model group and the siRNA-SAP group had different degrees of edema, inflammatory cell infiltration, and lobular structure damage, and the intestinal mucosa was damaged to a certain degree, and the villi were broken to varying degrees, but the damage in the siRNA-SAP group was lighter. The results of RT-PCR showed that the expression of lnc uc.173 in the intestinal tissues of the model SAP group was significantly lower than that of the NS group and the siRNA-NS group (2-ΔΔCt: 0.26±0.12 vs. 1.01±0.37, 0.67±0.32, both P < 0.05), while the expression of lnc uc.173 in the siRNA-SAP group was significantly higher than that in the SAP model group (2-ΔΔCt: 0.60±0.39 vs. 0.26±0.12, P < 0.05). Immunohistochemistry showed that ZO-1 and Occludin proteins in the NS group were distributed along the epithelial cells of the intestinal mucosa, showing a strong expression; ZO-1 and Occludin expressions were significantly reduced in the SAP model group and siRNA-SAP group, but the expressions in the siRNA-SAP group was higher than that in the SAP model group. Western blotting showed that the expression level of GSDMD protein in the intestinal tissues of the SAP model group was significantly higher than that of the NS group and the siRNA-NS group [GSDMD protein (GSDMD-N/ß-actin): 1.99±0.46 vs. 1, 1.00±0.78, both P < 0.05]. Compared with the SAP model group, the expression of GSDMD protein in the siRNA-SAP group was significantly decreased [GSDMD protein (GSDMD-N/ß-actin): 1.42±0.42 vs. 1.99±0.46, P < 0.05]. CONCLUSIONS: The systemic inflammatory response and intestinal mucosal barrier damage of SAP mice may be related to the increase of GSDMD expression in intestinal tissues. GSDMD mediates cell pyrolysis to promote the release of inflammatory factors, cause intestinal injury, and down-regulate the expression of intestinal epithelial cell tight junction proteins such as ZO-1 and Occludin, resulting in intestinal mucosal damage.

Downregulating Gasdermin D Reduces Severe Acute Pancreatitis Associated with Pyroptosis.

BACKGROUND Intestinal injury plays a key role in the pathogenesis of severe acute pancreatitis (SAP). In this study, we investigated the protective function of downregulated Gasdermin D (GSDMD) in intestinal damage in a mouse model of severe acute pancreatitis (SAP). MATERIAL AND METHODS Twenty-four healthy male C57BL/6 mice were randomly divided into 4 groups - the NS group, the siRNA-NS group, the SAP group, and the siRNA-SAP group - with 6 mice in each group. SAP was induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide. The pathological changes of pancreatic and the intestinal mucosa and the relative gene and protein expressions in each group were compared, and the levels of GSDMD and serum IL-1ß and IL-18 were evaluated after induction of the SAP model. RESULTS The mice in the SAP group were in more serious condition than those in the siRNA-SAP group, with various degrees of edema and hemorrhage in the intestinal tract. Under an optical microscope, the pathological changes of pancreatic tissue such as edema, inflammatory cell infiltration, and the damage of lobular structural were gradually increased in the SAP group and the siRNA-NS group. In addition, intestinal mucosal damage and intestinal villus breakage were found in the SAP group and the siRNA-NS group, and the latter was lighter than the former. Compared with the SAP group, the level of GSDMD protein expression in the siRNA-SAP group was lower, and the serum levels of IL-1ß and IL-18 were higher in the SAP group and siRNA-SAP group (P<0.05). Immunohistochemical analysis showed the occludin and ZO-1 proteins in the NS group had a strong brown linear signal, while the brown-positive signals were weaker in the siRNA-SAP group and the SAP group. CONCLUSIONS Downregulating GSDMD protein can reduce pancreatitis associated with pyroptosis.

Intracavernosal Adeno-Associated Virus-Mediated S100A1 Gene Transfer Enhances Erectile Function in Diabetic Rats by Promoting Cavernous Angiogenesis via VEGF-A/VEGFR2 Signaling.

INTRODUCTION: Novel therapeutic targets for diabetes-induced erectile dysfunction (DED) are urgently needed. Previous studies have proved that S100A1, a small Ca2+-binding protein, is a pluripotent regulator of cardiovascular pathophysiology. Its absence is associated with endothelial dysfunction, the central event linking cardiovascular changes in diabetes. However, the role of S100A1 in DED remains unknown. AIM: To explore the effect and underlying mechanisms of S100A1 in restoring erectile function in type I diabetic rat model. METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin and then screened by apomorphine (APO) to confirm erectile dysfunction. Rats that met the criteria of penile erection were marked as APO-positive; otherwise, the result was APO-negative. In experiment 1, S100A1 gene expression alterations in the corpus cavernosum in moderate and established stages of DED were analyzed. In experiment 2, S100A1 and control GFP gene were delivered into the corpus cavernosum in APO-negative rats by adeno-associated virus (AAV) serotype 9. Erectile function was assessed at 4 weeks after gene therapy. MAIN OUTCOME MEASURES: Erectile response, histologic and molecular alterations. RESULTS: S100A1 protein was localized to the area surrounding the cavernosal sinusoids in the penis, and it was gradually downregulated synchronized with the progression of DED. Compared with an injection of AAV-GFP, a single injection of AAV-S100A1 significantly restored erectile function in diabetic rats. S100A1 overexpression significantly upregulated the expression of endogenous VEGF-A, promoted VEGFR2 internalization, and subsequently triggered the protein kinase B-endothelial nitric oxide synthase pathway in diabetic erectile tissues. Marked increases in nitric oxide and endothelial content were noted in AAV-S100A1-treated diabetic rats. CLINICAL IMPLICATIONS: Local S100A1 overexpression may be an alternative therapy for DED and should be further investigated by future clinical studies. STRENGTH & LIMITATIONS: This is the first study demonstrating the angiogenic role of S100A1 in DED, but does not preclude the contribution of the effects of S100A1 in other tissues such as the neuronal tissue on the functional effects observed in erectile responses. CONCLUSION: The decreased expression of S100A1 during hyperglycemia might be important in the development of erectile dysfunction. S100A1 may play a potential role in restoring erectile function in rats with DED through modulating cavernous angiogenesis. Yu Z, Zhang Y, Tang Z, et al. Intracavernosal Adeno-Associated Virus-Mediated S100A1 Gene Transfer Enhances Erectile Function in Diabetic Rats by Promoting Cavernous Angiogenesis via VEGF-A/VEGFR2 Signaling. J Sex Med 2019;16:1344-1354.

Overexpression of heme oxygenase-1 in coronary atherosclerosis of Japanese autopsies with diabetes mellitus: Hisayama study.

Few studies regarding the topographical expression of heme oxygenase-1 (HO-1) and its pathophysiological role in human coronary atherosclerotic lesions, particularly in relation to type 2 diabetes mellitus (DM) and intimal angiogenesis, have been reported. HO-1 expression was immunohistochemically examined in 312 tissue blocks of coronary arteries obtained from 53 Japanese autopsy cases in Hisayama cohort study that included 19 diabetic subjects and 34 age- and sex-matched non-diabetic subjects (56-93 years old, mean+/-S.D.: 73+/-10). The HO-1 was ubiquitously distributed in atherosclerotic intima, and was mainly expressed by macrophages and endothelial cells, and partly by smooth muscle cells. The prevalence of HO-1 expression increased as the lesion type (as classified by the American Heart Association (AHA) Committee) and stenotic grade progressed (p<0.0001), and was significantly higher in diabetic than in non-diabetic subjects (p<0.01). This HO-1 overexpression was associated with greater CD-68-positive macrophage infiltration (p=0.005). Interestingly, the distribution of HO-1-positive cells was accentuated in coronary atherosclerotic lesions with intimal microvessels in diabetic subjects (p<0.05), particularly those with hypercholesterolemia (p<0.05), and was preferentially distributed in the shoulder region of atherosclerotic lesion type IV in the AHA classification (p<0.01). In conclusion, HO-1 expression was distributed in overall human coronary atherosclerotic lesions, particularly in diabetic subjects, indicating that HO-1 expression is intimately associated with atherogenesis and may play an important role as an adaptive molecule in the inflammatory-repair process. The association of HO-1 overexpression with a greater extent of intraplaque angiogenesis suggests a multi-faceted role for HO-1 in modulating the progression of atherosclerosis.

Preparation of poly(DL-lactide-co-glycolide) microspheres encapsulating all-trans retinoic acid.

Poly(DL-lactide-co-glycolide) (PLGA) microspheres containing all-trans retinoic acid (atRA) were prepared by o/w solvent evaporation method and various preparation parameters, such as poly(vinyl alcohol) (PVA) concentration in aqueous solution, PVA MW, drug weight, solvent, polymer MW, and polymer weight, on the characteristics of microspheres and drug release were investigated. PVA concentration in water phase was a critical factor in making microspheres consistently with smooth surface and round shape. In our study, at least 2% (w/v) of PVA in aqueous solution was necessary for making microspheres with round shape. The particle size of microspheres ranged 10-100 microm. AtRA was slowly released from PLGA microspheres over 30 days. Sterilization of microspheres by ethylene oxide (EO) gas at 37 degrees C did not significantly affect the characteristics of drug release or its morphology. Cell growth inhibition of atRA was affected by preparation process of microspheres rather than the EO-gas sterilization process. These results indicate that PLGA microspheres containing atRA are acceptable for controlled release devices for use in the treatment of brain tumor.