Efficacy of zinc oxide nanoparticles in attenuating pancreatic damage in a rat model of streptozotocin-induced diabetes

Zinc oxide nanoparticles (ZnO NPs) therapy is a promising strategy for treatment of several diseases. We aimed to investigate the therapeutic potential of ZnO NPs in ameliorating the histopathological and functional alterations in the pancreas of a rat model of streptozotocin-induced diabetes. Rats were randomized into control, diabetic and ZnO NPs-treated diabetic groups. Biochemical assays of blood glucose and serum insulin were performed. Pancreas specimens were processed for light and electron microscope examinations. ZnO NPs effectively reversed diabetes-induced pancreatic injury, as evidenced by the structural and ultrastructural improvement and confirmed by biochemical normalization of blood glucose and serum insulin.     

复发性实验性自身免疫性葡萄膜炎小鼠模型的诱导及其特点

目的 诱导复发性实验性自身免疫性葡萄膜炎(experimental autoimmune uveoretinitis,EAU)小鼠模型,评价其发生过程及特点.方法 完全弗氏佐剂(CFA)乳化的光感受器间维生素A类结合蛋白(IRBP) 161-180肽段免疫B10.RⅢ小鼠作为诱导组(35只),用CFA-PBS免疫小鼠作为对照组(6只).小鼠免疫后7、14、21、28、35 d裂隙灯显微镜和光学显微镜观察及评价眼部炎症发生、眼部表现和病理学变化;待炎症完全消失时,再次免疫小鼠,评价小鼠眼部炎症复发.结果 诱导组首次免疫后7d出现初发炎症,14 d炎症达高峰,随后炎症消退,至35 d完全消失.第35天进行再次免疫,36 d出现复发炎症,42 d达炎症高峰,随后炎症消退,但至观察期第96天部分鼠(1/5)仍维持炎症.眼部表现为睫状充血、前房渗出、瞳孔受损.病理学表现为视网膜和脉络膜炎性细胞浸润,血管炎、肉芽肿性炎,光感受器细胞层破坏,视网膜下渗出.对照组未见明显炎症.结论 建立的EAU呈现慢性复发性病程,其眼部表现和病理学特征与人类葡萄膜炎相似,可作为葡萄膜炎研究的新型动物模型.     

Whole-specimen histopathology: a method to produce whole-mount breast serial sections for 3-D digital histopathology imaging

AIMS: To develop a method for preparing diagnostic-quality, whole-mount serial sections of breast specimens while preserving 3-D conformation. This required supporting the fresh specimen prior to breadloafing and refining the conventional tissue processing method. The overall goal is to use digital images of whole-specimen histopathology to improve the estimation of extent of disease. METHODS AND RESULTS: To maintain a 3-D conformation, the specimen is suspended in 3.5% agar at 55 degrees C. The block is sliced at 5-mm intervals. Sectioning is performed after extended fixation in 4% formaldehyde from paraformaldehyde in 0.1 m Millonig's buffer, followed by paraffin processing using a non-routine schedule and extended paraffin infiltration. Whole-mount serial breast sections are produced with features of equal or superior quality to that which can be achieved using conventional methods. The method is compatible with some immunohistochemical stains but requires further optimization for others. CONCLUSIONS: The technique is currently suitable for research applications. With the reduction in processing time achievable with microwave-assisted processing, there is the potential for its use as a routine clinical method. This tool may improve the accuracy of margin estimates and identification of multifocality in breast cancer; further evaluation is necessary.     

Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review

BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.     

Formulation and in vivo assessment of terconazole-loaded polymeric mixed micelles enriched with Cremophor EL as dual functioning mediator for augmenting physical stability and skin delivery

The aim of the current study was to formulate terconazole (TCZ) loaded polymeric mixed micelles (PMMs) incorporating Cremophor EL as a stabilizer and a penetration enhancer. A 2³ full factorial design was performed using Design-Expert® software for the optimization of the PMMs which were formulated using Pluronic P123 and Pluronic F127 together with Cremophor EL. To confirm the role of Cremophor EL, PMMs formulation lacking Cremophor EL was prepared for the purpose of comparison. Results showed that the optimal PMMs formulation (F7, where the ratio of total Pluronics to drug was 40:1, the weight ratio of Pluronic P123 to Pluronic F127 was 4:1, and the percentage of Cremophor EL in aqueous phase was 5%) had a high micellar incorporation efficiency (92.98?±?0.40%) and a very small micellar size (33.23?±?8.00?nm). Transmission electron microscopy revealed that PMMs possess spherical shape and good dispersibility. The optimal PMMs exhibited superior physical stability when compared with the PMMs formulation of the same composition but lacking Cremophor EL. Ex vivo studies demonstrated that the optimal PMMs formula markedly improved the dermal TCZ delivery compared to PMMs lacking Cremophor EL and TCZ suspension. In addition, it was found that the optimal PMMs exhibited a greater extent of TCZ deposition in the rat dorsal skin relative to TCZ suspension. Moreover, histopathological studies revealed the safety of the optimal PMMs upon topical application to rats. Consequently, PMMs enriched with Cremophor EL, as a stable nano-system, could be promising for the skin delivery of TCZ.     

Inflammation in areas of fibrosis: The DeKAF prospective cohort

Inflammation in areas of fibrosis (i‐IFTA) in posttransplant biopsy specimens has been associated with decreased death‐censored graft survival (DC‐GS). Additionally, an i‐IFTA score ≥ 2 is part of the diagnostic criteria for chronic active TCMR (CA TCMR). We examined the impact of i‐IFTA and t‐IFTA (tubulitis in areas of atrophy) in the first biopsy for cause after 90 days posttransplant (n = 598); mean (SD) 1.7 ± 1.4 years posttransplant. I‐IFTA, present in 196 biopsy specimens, was strongly correlated with t‐IFTA, and Banff i. Of the 196, 37 (18.9%) had a previous acute rejection episode; 96 (49%) had concurrent i score = 0. Unlike previous studies, i‐IFTA = 1 (vs 0) was associated with worse 3‐year DC‐GS: (i‐IFTA = 0, 81.7%, [95% CI 77.7 to 85.9%]); i‐IFTA = 1, 68.1%, [95% CI 59.7 to 77.6%]; i‐IFTA = 2, 56.1%, [95% CI 43.2 to 72.8%], i‐IFTA = 3, 48.5%, [95% CI 31.8 to 74.0%]). The association of i‐IFTA with decreased DC‐GS remained significant when adjusted for serum creatinine at the time of the biopsy, Banff i, ci and ct, C4d and DSA. T‐IFTA was similarly associated with decreased DC‐GS. Of these indication biopsies, those with i‐IFTA ≥ 2, without meeting other criteria for CA TCMR had similar postbiopsy DC‐GS as those with CA TCMR. Those with i‐IFTA = 1 and t ≥ 2, ti ≥ 2 had postbiopsy DC‐GS similar to CA TCMR. Biopsies with i‐IFTA = 1 had similar survival as CA TCMR when biopsy specimens also met Banff criteria for TCMR and/or AMR. Studies of i‐IFTA and t‐IFTA in additional cohorts, integrating analyses of Banff scores meeting criteria for other Banff diagnoses, are needed.     

Antioxidant and hepatoprotective effects of Solanum xanthocarpum leaf extracts against CCl4-induced liver injury in rats

Context: Solanum xanthocarpum Schard. and Wendl. (Solanaceae) has been used in traditional Indian medicines for its antioxidant, anti-inflammatory, and antiasthmatic properties.

Objective: The present study demonstrates the antioxidant and hepatoprotective effects of S. xanthocarpum. On the basis of in vitro antioxidant properties, the active fraction from column chromatography of the methanol extract of S. xanthocarpum leaves (SXAF) was chosen as the potent fraction and used for hepatoprotective studies in rats.

Materials and methods: The antioxidant activity was evaluated by 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reducing power assays. Rats were pre-treated with 100 and 200?mg/kg b.w. of SXAF for 14?d with a single dose of CCl₄ in the last day. Hepatoprotective properties were determined by serum biochemical enzymes, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), antioxidant enzymes (SOD, CAT, GSH, and GST), and histopathology studies.

Results: SXAF exhibited significant antioxidant activity in scavenging free radicals with IC₅₀ values of 11.72?µg (DPPH) and 17.99?µg (ABTS). Rats pre-treated with SXAF demonstrated significantly reduced levels of serum LDH (1.7-fold), ALP (1.6-fold), and AST (1.8-fold). Similarly, multiple dose SXAF administration at 200?mg/kg b.w. demonstrated significantly enhanced levels of SOD (1.78?±?0.13), CAT (34.63?±?1.98), GST (231.64?±?14.28), and GSH (8.23?±?0.48) in liver homogenates. Histopathological examination showed lowered liver damage in SXAF-treated groups.

Discussion and conclusion: These results demonstrate that SXAF possesses potent antioxidant properties as well as hepatoprotective effects against CCl₄-induced hepatotoxicity.