The 6-mercaptopurine (6-MP) is an effective immunosuppressant and anti-cancer drug. However, the usage of 6-MP is limited due to its well-known side effects, such as myelotoxicity and hepato-renal toxicity. To curtail the potential toxic effects, we have used chitosan as a natural biodegradable and biocompatible polysaccharide to synthesize 6-Mercaptopurine-Chitosan Nanoparticles (6-MP-CNPs). The 6-MP-CNPssize, morphology, physicochemical interactions, and thermal stability were characterized using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC), respectively. The loading efficiency of the 6-MP in CNPs was estimated using LCMS/MS. Then, the 6-MP-CNPs were subjected to in vivo acute and sub-acute oral toxicity evaluations. The DLS and SEM analysis respectively indicated size (70.0 nm to 400.0 nm), polydispersity index (0.462), and zeta potential (54.9 mV) with improved morphology of 6-MP-CNPs. The FTIR and DSC results showed the efficient interactive and stable nature of the 6-MP-CNPs, which sustained the drug-delivery process. The loading efficiency of 6-MP-CNPs was found to be 25.23%. The chitosan improved the lethal dose (LD50 cut off) of 6-MP-CNPs (1000 mg/kg b.w) against 6-MP (500 mg/kg b.w) and also significantly (p ≤ 0.05) reduces the toxic adverse effect (28-day repeated oral dose) on hemato-biochemical and hepato-renal histological profiles. The findings suggest that chitosan, as a prime drug-delivery carrier, significantly alleviates the acute and sub-acute toxic effects of 6-MP.

In the present study, we compared the effect of diabetic pregnancy on the rectus abdominis muscle (RAM) in humans and rats. We hypothesized that our animal model could provide valuable information about alterations in the RAM of women with Gestational Diabetes (GDM). Newborns female rats (n = 10/group) were administered streptozotocin (100 mg/kg body weight) subcutaneously and were mated on reaching adulthood, to develop the mild hyperglycemic pregnant (MHP) rat model. At the end of pregnancy, the mothers were sacrificed, and the RAM tissue was collected. Pregnant women without GDM (non-GDM group; n = 10) and those diagnosed with GDM (GDM group; n = 8) and undergoing treatment were recruited, and RAM samples were obtained at C-section. The RAM architecture and the distribution of the fast and slow fibers and collagen were studied by immunohistochemistry. No statistically significant differences in the maternal and fetal characters were observed between the groups in both rats and women. However, significant changes in RAM architecture were observed. Diabetes in pregnancy increased the abundance of slow fibers and decreased fast fiber number and area in both rats and women. A decrease in collagen distribution was observed in GDM women; however, a similar change was not observed in the MHP rats. Our results indicated that pregnancy- associated diabetes- induced similar structural adaptations in the RAM of women and rats with slight alterations in fiber type number and area. These findings suggest that the MHP rat model can be used for studying the effects of pregnancy-associated diabetes on the fiber structure of RAM.

Background: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. Methods: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24–26 weeks, with a follow-up at 34–38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24–48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. Discussion: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.