[Effect analysis of the modified wire-loop snare technique in retrieving severely tilted inferior vena cava filters].

Objective: To examine the application effect of the modified wire-loop snare technique in retrieving severely tilted inferior vena cava filters (IVCF). Methods: The clinical data of 18 patients (12 males and 6 females, aged (62.1±13.1) years (range: 29 to 78 years)) who underwent the modified wire-loop snare technique to retrieve IVCF at the Affiliated Hospital of Qingdao University, Qingdao Eighth People's Hospital, and Jimo District Hospital of Traditional Chinese Medicine from November 2017 to April 2022 were retrospectively analyzed. The applied filters included drum-type filters (OptEase in 7 cases, Aegisy in 2 cases) and conical filters (Celect in 6 cases and Denali in 3 cases). Preoperative CT angiography and intraoperative digital subtraction angiography showed that the filter was severely tilted and the hook was covered by hyperplastic intima of the vena cave vein. A modified wire-loop snare technique was used to retrieve drum-type filters and conical filters via femoral and jugular vein approaches, respectively. After successful puncture, the long sheath was placed, the 4 F (1 F≈0.33 mm) vertebral catheter and a snare were inserted through the long sheath, and the 5 F pigtail catheter was inserted simultaneously to guide a 0.035 inch soft guide-wire (260 cm in length) to pass through the top of the filter and turning back. The tip of the soft guide-wire was snared by the vertebral catheter and pulled out of the sheath. The 4 F vertebral catheter was inserted following the tip of the guide-wire to form a wire-loop using the vertebral catheter and the pigtail catheter. After fixing the tip and tail of the soft guide-wire in vitro, the long sheath was pushed forward to cut the hyperplastic intima and the hook was pulled away from the vena cava wall to retrieve the filter under the support of two catheters. Results: The filters were successfully retrieved in 17 cases, the operation time was (25.5±8.7) minutes (range: 15 to 45 minutes), no complication occured. The hook of one filter (Celect) penetrated out of the vena vava wall and the wire-loop could not pull the hook back into the vena cava. Then the filter was removed by laparotomy. Conclusion: The modified wire-loop snare technique could retrieve the severely tilted retrivable drum-type filters and conical filters, even when serve adhesion exists between the filter and the vena cava wall.

Preoperative urinary function does not predict postoperative acute urinary retention in men after rectal resection.

AIM: Acute urinary retention (AUR) is a well-known complication after rectal surgery. It can be associated with additional morbidity. Causes of postoperative AUR are often multifactorial - involving patient-, pathology- and treatment-related factors. A proportion of men undergoing total mesorectal excision (TME) have preexisting urinary dysfunction and this may predispose to AUR. The aim of this study was to prospectively assess the influence of preoperative urinary function on postoperative AUR in men undergoing TME. METHOD: A prospective multicentre cohort study was conducted. All adult men undergoing rectal resection between June 2016 and January 2018 were recruited. Combined pelvic resections, inability to void per urethra and emergency surgery were excluded. Preoperative urinary function was assessed with uroflowmetry, prostate ultrasound and the International Prostate Symptom Score (IPSS). The incidence of postoperative AUR, urinary tract infection (UTI) and length of hospital stay (LOS) were measured. RESULTS: Seventy-seven patients (mean age 61 years) were recruited. The overall incidence of AUR was 21%. Preoperative urinary function, IPSS and past urological history were not predictive for postoperative AUR. AUR was not associated with UTI and did not affect LOS. Patients with UTI had a higher intravesical protrusion of the prostate. CONCLUSION: Preoperative urinary dysfunction in men is not predictive of postoperative AUR after TME. It should not preclude early trial of void after TME. AUR did not predispose to UTI, nor did it prolong LOS.

Lack of association between CARD10/CARMA3 tag SNPs and psoriasis vulgaris in the southern Chinese population.

Previously, we determined that the CARD11 rs4722404 single nucleotide polymorphism (SNP) increases risk of early-onset psoriasis vulgaris (PsV). Moreover, the CARD14 gene polymorphism c.C2458T (p.Arg820Trp) is associated with clinical features of this disease. CARMA1/CARD11, CARMA2/CARD14, and CARMA3/CARD10 are conserved across many species and constitute a family of proteins, all of the members of which contain various functional domains characteristic of this group. The NF-κB signaling pathway, regulated by the CARMA family of scaffold proteins and its eponymous component, is a crucial mediator in the pathogenesis of psoriasis. However, little is known about the association between CARMA3/CARD10 and PsV. The aim of this study was to evaluate the relationship between the gene encoding this protein and risk of PsV in the southern Han Chinese population. Genomic DNA from 568 individuals of southern Chinese origin, including 355 patients with PsV and 213 control subjects, was analyzed. We selected seven tag SNPs in the CARMA3/CARD10 gene and genotyped them by the SNaPshot assay. Our results identified no significant association between these SNPs and PsV in the Chinese population examined. Future studies should focus on the potential function of the CARMA3/CARD10 gene in the pathogenesis of PsV.

Association between atopic dermatitis-related single nucleotide polymorphisms rs4722404 and psoriasis vulgaris in a southern Chinese cohort.

Genome-wide association studies have identified a single nucleotide polymorphism (SNP), rs4722404, in the caspase recruitment domain family member 11 (CARD11) gene, which is associated with atopic dermatitis. Previous genetic studies have also reported genomic similarities between psoriasis and atopic dermatitis. However, little is known regarding the association between rs4722404 and psoriasis vulgaris (PsV). The aim of this study was to evaluate the relationship between rs4722404 and the risk and clinical features of PsV in a southern Chinese Han cohort. This hospital-based case-control study included 355 patients with PsV and 213 control subjects (N = 568); the samples were analyzed using a standard SNaPshot assay. We identified no association between the SNP and risk of PsV. However, a stratified analysis according to the age of onset, family history, and psoriasis area and severity index sub-phenotypes revealed a significant correlation between the C allele and CC+CT genotype of rs4722404 and an increased risk of early-onset PsV (≤40 years) compared to that of late-onset PsV (>40 years) (odds ratio, OR = 1.486; P = 0.026 for C allele and OR = 1.718, P = 0.023 for CC+CT genotype). The results of this study suggested that the SNP rs4722404 in CARD11 could increase the risk of early-onset PsV. Further studies must analyze the potential function of CARD11 in the pathogenesis of PsV.

The common CARD14 gene missense polymorphism rs11652075 (c.C2458T/p.Arg820Trp) is associated with psoriasis: a meta-analysis.

Recent genetic evidence suggests a robust association of the CARD14 single nucleotide polymorphism rs11652075 (c.C2458T/p.Arg820Trp) and other rare mutations in this gene with psoriasis. To assess whether combined data support the relationship between CARD14 rs11652075 and susceptibility to this disease, we conducted a meta-analysis. PubMed (MEDLINE), EMBASE, Web of Science, and the Cochrane Library were searched for relevant papers published in English. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effect models. Heterogeneity between studies was assessed using the Cochran's Q and I2 statistics. A total of five published studies, including 32,807 psoriasis patients and 45,458 controls, met our inclusion criteria and were included in the meta-analysis. The pooled OR of the association between the minor allele of this polymorphism and psoriasis was 0.877 (95%CI = 0.834-0.922; P < 0.001). In a stratified analysis, pooled ORs relating to European and Asian ancestry were 0.883 (95%CI = 0.822-0.948) and 0.872 (95%CI = 0.812-0.936), respectively. Those calculated for studies with case sample sizes above and below 1000 were 0.912 (95%CI = 0.870- 0.956) and 0.824 (95%CI = 0.734-0.924), respectively. No publication bias was present, and the exclusion of any single dataset did not substantially alter the corresponding pooled ORs. Due to the limited data available regarding clinical classification of cases and genotypes, subgroup stratification by clinical type was not performed. Our results demonstrate a significant association between the CARD14 rs11652075 polymorphism and psoriasis.

The TNFAIP3 polymorphism rs610604 both associates with the risk of psoriasis vulgaris and affects the clinical severity.

BACKGROUND: Genome-wide association studies in white and Chinese Han populations have found that the single-nucleotide polymorphism (SNP) rs610604, at the tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) locus, is associated with psoriasis, and is also associated with response to TNF blockade in psoriasis. AIM: To examine whether this SNP is also associated with the clinical traits of psoriasis vulgaris (PV). METHODS: A hospital-based case-control study was performed, which involved 647 subjects [351 patients with PV and 296 healthy controls (HC)]. The rs610604 variants were typed using a SNaPshot assay. RESULTS: Both the G allele and the dominant model genotype (GG + GT) of rs610604 were associated with risk of PV (OR = 1.53; P = 0.01 and OR = 1.68, P < 0.01, respectively). In genotype-phenotype analysis, both the G allele and the GG + GT genotype were also associated with the clinical severity of PV. Severe cases [Psoriasis Area and Severity Index (PASI) > 6] had a higher frequency of the G allele and the GG + GT genotype compared with mild cases (PASI ≤ 6) (OR = 2.03, P = 0.001 and OR = 2.46, P < 0.001, respectively). In addition, rs610604 was significantly associated with almost all of the phenotypes in subphenotype-control analyses. CONCLUSIONS: SNP rs610604 in the TNFAIP3 locus is associated with the clinical severity of PV in a Chinese Han population.

Case report. Novel and recurrent COL7A1 mutations in Chinese patients with dystrophic epidermolysis bullosa pruriginosa.

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of dystrophic epidermolysis bullosa (DEB). This disease is characterized by severe itching, lichenoid nodules or prurigo-like lesions, and linear scarring with a predilection for the extensor limbs. Pathogenic mutations in the type VII collagen alpha 1 (COL7A1) gene have been identified. We analyzed mutations in the COL7A1 gene in a Chinese family including 5 affected individuals with typical DEB-Pr and in a patient previously reported with sporadic DEB-Pr. The entire coding region and exon-intron boundaries of COL7A1 were detected by polymerase chain reaction and direct sequencing. We identified one novel heterozygote mutation (c.6842G>T, p.G2281V) and a second mutation (c.5443G>A, p.G1815R) reported previously in patients with DEB. Our findings contribute to the COL7A1 mutation database and further reveal the genetic and phenotypic heterogeneity of DEB-Pr.

Association between hypoxia-inducible factor-1a levels in serum and synovial fluid with the radiographic severity of knee osteoarthritis.

Osteoarthritis (OA) is primarily characterized by articular cartilage degradation. Hypoxia-inducible factor-1a (HIF-1a), a subunit of the basic helix-loop-helix-containing PER-ARNT-SIM (PAS) domain transcription factors, plays a vital role in the survival of articular chondrocytes to the hostile hypoxic microenvironment and complicates the progression of OA. In this study, we examined whether HIF-1a levels in the serum and synovial fluid (SF) of patients with knee OA were increased and whether the increase was correlated with the radiographic severity of the disease. A total of 278 knee OA patients and 203 healthy controls were enrolled in this study. Knee OA radiographic grading was performed according to Kellgren-Lawrence (KL) grading system by evaluating X-ray changes observed on anteroposterior knee radiography. HIF-1a levels in the serum and SF were determined using an enzyme-linked immunosorbent assay. Serum HIF-1a levels in patients with knee OA were higher than those in healthy controls. Knee OA patients with KL grade 4 showed significantly elevated HIF-1a levels in the serum and SF compared with those with KL grades 2 and 3. Knee OA patients with KL grade 3 showed significantly higher SF levels of HIF-1a than those with KL grade 2. HIF-1a levels in the serum and SF of knee OA patients were significantly correlated with disease severity according to KL grading criteria. HIF-1a levels in the serum and SF were closely related to the radiographic severity of OA and may serve as an alternative biomarker for the progression and prognosis of knee OA.

Leptin levels in patients with psoriasis: a meta-analysis.

BACKGROUND: There have been inconsistent results reported for leptin levels in patients with psoriasis. AIM: To evaluate leptin levels in patients with psoriasis using a meta-analysis of studies comparing leptin levels in controls and in patients with psoriasis. METHODS: PubMed (MEDLINE), EMBASE and the Cochrane Library were searched for relevant papers published in English. Pooled weighted mean differences (WMDs) and 95% CIs were calculated using random-effects and fixed-effects models. Heterogeneity between studies was assessed using the Cochran Q and I(2) statistics. RESULTS: In total, 11 studies, comprising 773 patients with psoriasis and 570 healthy controls, were identified. Leptin levels were significantly higher in patients with psoriasis compared with controls (WMD = 7.24, 95% CI 4.55-9.93; P < 0.001). On stratified analysis, significant differences in leptin levels between patients with psoriasis and controls were reported only in serum samples (P < 0.001), and not in plasma samples (P = 0.025). Sensitivity analysis showed that there were no changes in the direction of effect when any one study was excluded. No publication bias was detected. CONCLUSIONS: Leptin levels are higher in patients with psoriasis compared with those in controls. Future studies are warranted to clarify the association between leptin levels and the pathomechanism of psoriasis.

A novel insertion mutation in the ADAR1 gene of a Chinese family with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules that are mainly present on the dorsal portions of the extremities. The DSH locus was mapped to chromosome 1q11-q12 and, subsequently, pathogenic mutations in the double-stranded RNA-specific adenosine deaminase (ADAR1) gene were identified. We performed a mutational analysis of the ADAR1 gene in a Chinese family that included three individuals affected with typical DSH phenotypes. Mutations within the entire coding region and the exon-intron boundaries of ADAR1 were detected and confirmed by polymerase chain reaction and direct sequencing, respectively. An insertion mutation within exon 12, c.3035_3036insC (p.P1012fsX1017), was identified in all family members affected by DSH, but not in the healthy members or 100 unrelated controls. This finding improves our understanding of the role of ADAR1 in DSH.

Comparisons of clinical features of HLA-DRB1*07 positive and negative vitiligo patients in Chinese Han population.

BACKGROUND: Human leucocyte antigen (HLA)-II alleles have been found to be associated with vitiligo in different populations, and several studies also suggested that HLA class II alleles/haplotypes were associated with a different type vitiligo. Of HLA class II alleles, DRB1*07 has consistently shown a positive association with vitiligo in Chinese Han population. OBJECTIVE: To further explore the relationship between DRB1*07 and vitiligo and to evaluate the DRB1*07 effect on the clinical features of vitiligo in Chinese Han population. METHODS: This study investigated DRB1*07 allele distribution in 1178 unrelated Chinese vitiligo patients and 1743 healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07 positive and DRB1*07 negative patients. RESULTS: The analysis of the 1178 cases and 1743 controls revealed a highly association between DRB1*07 allele and vitiligo [odds ratio (OR) = 1.97, P = 2.13 × 10(-17) ]. DRB1*07 positive patients had early disease onset (OR = 1.49, P = 0.001), higher frequency of family history (OR = 1.44, P = 0.006) compared with DRB1*07 negative patients. CONCLUSIONS: The DRB1*07 showed significant association with vitiligo in the study population. This study confirmed that DRB1*07 positive patients had some obvious clinical differences from DRB1*07 negative patients in the Chinese Han population.

The effect of overweight and obesity on psoriasis patients in Chinese Han population: a hospital-based study.

BACKGROUND: Accumulating evidence indicates that psoriasis is associated with increased risk of overweight and obesity. However, few studies have investigated this relationship in Chinese Han population. OBJECTIVE: The aim of this study was to explore the relationship between overweight/obesity and psoriasis and to evaluate the overweight/obesity effect on the clinical features of psoriasis in Chinese Han population. METHODS: A hospital-based study was conducted, which involved in 4452 patients and 1166 controls of Chinese Han through epidemiological investigation. Controls used in the study were individuals without psoriasis from health examination centre, and other skin disease patients from outpatient department. RESULTS: Compared with the control group, a significantly greater prevalence of overweight and obesity was observed in psoriasis patients. The estimated ORs were 1.301 (95% CI, 1.105-1.531) and 1.680 (95% CI, 1.134-2.491) respectively. The disease severity of psoriasis measured by psoriasis area and severity index (PASI) was statistically correlated with body mass index (BMI) (r = 0.184, P < 0.01). Moreover, a high proportion of overweight patients had affected hands or/and feet, buttocks, trunk, legs, arms and arthritis (P < 0.01). CONCLUSIONS: Our study suggested that psoriatic patients have a higher prevalence of overweight and obesity compared with non-psoriatic patients in Chinese Han population. Overweight and obesity has different risk effect on severity and manifestations of psoriasis and might be useful for better evaluating psoriasis clinically.

RNA interference silences the human papillomavirus 6b/11 early gene E7 in vitro and in vivo.

BACKGROUND: RNA interference (RNAi) is a potential therapeutic tool in the treatment of various diseases, such as cancers and viral infections. Silencing of E7 genes is an effective method to suppress human papilloma virus (HPV)-related tumours. AIM: To determine the therapeutic potential of RNAi in controlling condyloma acuminatum (CA). METHODS: Small interfering (si)RNA duplexes or small-hairpin (sh)RNA-expressing plasmids targeting the E7 genes of HPV-6b or HPV-11were inoculated into cultured E7-expressing cells via cationic liposomes, or into E7 gene-expressing mouse tumour models intratumorally or intravenously. Experiments were performed in triplicate and E7 mRNA level was analysed by real-time PCR. RESULTS: The in vitro experiments found that both siRNAs and shRNA-expressing plasmids reduced the mRNA levels of HPV-6b or HPV-11 E7 to 20-40% at the optimum dosage of 25-50 nmol/L for siRNAs and 0.1-0.2 microg/mL for shRNA-expressing vectors. The optimum time for this to happen was 72 h. E7 mRNA expression in tumour models was reduced to 45-50% after three intratumural injections. Intratumoral injections of RNAi effectors induced greater inhibition than did intravenous injections. CONCLUSIONS: We conclude that HPV-6b/11 E7 gene expression can be specifically modulated by RNAi, which may provide a useful method in the management of CA.

Expression of Foxp3+CD4+CD25+ regulatory T cells and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of patients with condyloma acuminatum.

BACKGROUND: Condyloma acuminatum (CA) is a disease that appears as proliferative lesions of the genital epithelium caused by human papillomavirus (HPV) infection. The balance between type 1 and type 2 T-cell subsets in patients with CA is thought to modulate antiviral immunity. CD4+CD25+ regulatory T cells (Tregs) inhibit proliferation and cytokine production by both T-helper (Th)1 and Th2 cells and reversibly suppress CTL-mediated immunity. A better understanding of the mechanisms of T-cell regulation in CA might help in developing more effective therapeutic strategies. Objective. To evaluate the balance of Th1/Th2 and Tc1/Tc2 and to assess their correlation with changes in number of Tregs in CA. METHODS: The percentage of Th1, Th2, Tc1, Tc2 and Tregs were detected by flow cytometry after intracellular staining for cytokines (interferon-gamma and interleukin-4) and Foxp3 of T lymphocytes in the peripheral blood of 30 patients and 20 healthy volunteers. RESULTS: Patients with CA showed a decreased proportion of Th1 and Tc1 cells and a decreased ratio of Th1/Th2 and Tc1/Tc2. In particular, strikingly decreased ratios of Th1/Th2 were found in 15 patients with relapsed CA (P < 0.01). The mean +/- SD number of Foxp3+CD4+CD25+ Tregs increased significantly in patients with CA (3.37 +/- 1.03%) and patients with relapsed CA (4.68 +/- 1.17%) compared with healthy controls (1.18 +/- 0.53%) (P < 0.001). CONCLUSION: Tregs appear to downregulate cytokine expression in both Tc1 and Th1 subsets of effector T cells, which may be responsible for antivirus responses.

Complete atrioventricular block associated with dapsone therapy: a rare complication of dapsone-induced hypersensitivity syndrome.

Dapsone is still widely used for a range of infectious and inflammatory diseases. A potential severe side-effect, known as dapsone-induced hypersensitivity syndrome (DHS), may occur. DHS is characterized by fever, skin rashes, lymphadenopathy and multiorgan dysfunction manifesting as hepatitis, cholangitis, pneumonitis, colitis, thyroiditis and myocarditis. However, DHS-associated complete atrioventricular block has not previously been reported. We describe here a 45-year-old Chinese woman who developed DHS after 5 weeks of dapsone therapy for pustular palmoplantar psoriasis. In addition to typical DHS symptoms, she experienced several episodes of syncope as a result of complete atrioventricular block which was successfully reversed with a permanent pacemaker implantation.

Primary peritonectomy/HIPEC for disseminated peritoneal adenomucinosis achieves much lower recurrence rates and better survival than secondary procedures.

BACKGROUND: Two main treatment options are available for pseudomyxoma peritonei (PMP) and disseminated peritoneal adenomucinosis (DPAM)--incomplete cytoreductive (debulking) surgery and peritonectomy with intraperitoneal chemotherapy. Several studies have demonstrated improved survival with peritonectomy. This study analyses outcome following peritonectomy in patients undergoing a primary procedure compared to those who have had previous debulks. METHODS: Between April 1997 and May 2008, 63 patients underwent peritonectomy for DPAM--38 had had previous debulk(s) and 25 underwent primary peritonectomy. Patients were followed-up at three- to six-monthly intervals postoperatively, with a mean follow-up time of 21 and 34 months, respectively. RESULTS: Mean survival for patients undergoing primary peritonectomy was 109.8 months. Mean survival for patients with previous debulks was 49.2 months (p=0.027). Five-year survival was 95.5% in the primary peritonectomy group and 67.5% in the previous debulk group. CONCLUSION: Disease recurrence after primary peritonectomy for DPAM is significantly less frequent than after secondary peritonectomy.

Pressure-induced enhancement of thermoelectric power factor in pristine and hole-doped SnSe crystals.

We evaluate the influence of pressure on the thermoelectric power factors PF ≡ S 2 σ of pristine and Na-doped SnSe crystals by measuring their electrical conductivity σ(T) and Seebeck coefficient S(T) up to ∼22 kbar with a self-clamped piston-cylinder cell. For both cases, σ(T) is enhanced while S(T) reduced with increasing pressure as expected, but their imbalanced variations lead to a monotonic enhancement of PF under pressure. For pristine SnSe, σ(290 K) increases by ∼4 times from ∼10.1 to 38 S cm-1, while S(290 K) decreases by only ∼12% from 474 to 415 µV K-1, leading to about three-fold enhancement of PF from 2.24 to 6.61 µW cm-1 K-2, which is very close to the optimal value of SnSe above the structural transition at ∼800 K at ambient pressure. In comparison, the PF of Na-doped SnSe at 290 K is enhanced moderately by ∼30% up to 20 kbar. In contrast, the PF of isostructural black phosphorus with a simple band structure was found to decrease under pressure. The comparison with black phosphorus indicates that the multi-valley valence band structure of SnSe is beneficial for the enhancement of PF by retaining a large Seebeck coefficient under pressure. Our results also provide experimental confirmation on the previous theoretical prediction that high pressure can be used to optimize the thermoelectric efficiency of SnSe.

Preparation, characterization and nasal delivery of alpha-cobrotoxin-loaded poly(lactide-co-glycolide)/polyanhydride microspheres.

In this study, alpha-cobrotoxin was incorporated into the microspheres composed of poly(lactide-co-glycolide) (PLGA) and poly[1,3-bis(p-carboxy-phenoxy) propane-co-p-(carboxyethylformamido) benzoic anhydride] (P(CPP:CEFB)) and intranasally delivered to model rats in order to improve its analgesic activity. The microspheres with high entrapment efficiency (>80%) and average diameter of about 25 microm could be prepared by a modified water-in-oil-in-oil (w/o/o) emulsion solvent evaporation method. Scanning electron micrograph (SEM) study indicated that P(CPP:CEFB) content played a considerable role on the morphology and degradation of the microspheres. The presence of P(CPP:CEFB) in the microspheres increased their residence time at the surface of the nasal rat mucosa. The toxicity of the composite microspheres to nasal mucosa was proved to be mild and reversible. A tail flick assay was used to evaluate the antinociceptive activity of the microspheres after nasal administration. Compared with the free alpha-cobrotoxin and PLGA microspheres, PLGA/P(CPP:CEFB) microspheres showed an apparent increase in the strength and duration of the antinociceptive effect at the same dose of alpha-cobrotoxin (80 microg/kg body weight).

In vitro and in vivo studies of cyclosporin A-loaded microspheres based on copolymers of lactide and epsilon-caprolactone: comparison with conventional PLGA microspheres.

A hydrophobic peptide, cyclosporin A (CyA), was incorporated in microspheres based on poly(lactide-b-epsilon-caprolactone) (P(LA-b-CL), LA/CL (in molar ratio): 78.7/21.3 and 48.1/51.9) and poly(lactide-co-glycolide) (PLGA, LA/GA: 80/20) using oil-in-water (O/W) emulsion solvent evaporation method. The microspheres were characterized by SEM, DSC and X-ray diffraction, and CyA release rate was determined by HPLC. It was revealed that CyA can be efficiently loaded into all the microspheres (exceed 96%). Compared to PLGA microspheres, P(LA-b-CL) microspheres liberated CyA more rapidly. Within the first day, about 75, 50 and 12% of CyA released from P(LA-b-CL) (48.1/51.9), P(LA-b-CL) (78.7/21.3) and PLGA microspheres, respectively, which can be attributed to the partial crystallization occurring in P(LA-b-CL) microspheres. CyA levels in whole blood were also tested. In comparison with PLGA microspheres, P(LA-b-CL) microspheres provided a higher blood level of CyA. The maximum CyA concentration in whole blood (approximately 520, 450 and 400 ng ml(-1) for P(LA-b-CL) (48.1/51.9) P(LA-b-CL) (78.7/21.3) and PLGA microspheres, respectively) was reached at the second day post administration. And then P(LA-b-CL) microspheres showed a constant CyA level (about 100-200 ng ml(-1)) for extended periods of time (several weeks). Such CyA-loaded P(LA-b-CL) microspheres displaying higher CyA concentration during the first few days and similar constant blood CyA level thereafter showed more advantages than those prepared with PLGA and could meet clinical needs more efficiently.

Salicylic acid and PEG-contained polyanhydrides: synthesis, characterization, and in vitro salicylic acid release.

Poly [bi(o-carboxyphenyl)adipate-polyethylene glycol] anhydrides--P(BOCA-PEG)--polymeric drugs were synthesized and characterized by Fourier transformed infrared spectroscopy, NMR, DSC, gel permeation chromatography, etc. Salicylic acid loading efficiency of these polymers ranged from 43.5% to 71.3%, which was much higher than that of other polymeric drugs with salicylic acid. The in vitro release of salicylic acid from the polymers was carried out in buffer conditions with different pH values and and rat gastrointestinal contents. The results showed the release rate of salicylic acid increased with the increase of PEG content in the polymers and the increase of pH value of degradation buffer solution. The rat cecal contents also greatly promoted the release of salicylic acid. In 0.1M phosphate buffer solution at pH8.0, 37 degrees C containing 5% rat cecal contents, P(BOCA-PEG200)(80:20) had 15% salicylic acid released in 21 hr, indicating its potential use in colon-specific salicylic acid delivery.