Syringomatous adenoma of the nipple: report of a case

Syringomatous adenoma of the nipple is a rarely encountered neoplasm of the breast with histological features similar to eccrine syringoma of the skin. This tumour which is locally invasive with high potential for recurrence if incompletely excised is considered benign and a complete excision is sufficient. Hence it deserves recognition by pathologists and surgeons for appropriate management. We report a case of syringomatous adenoma of the nipple in a postmenopausal diabetic woman who was incidentally found to have a subareolar mass in her right breast. Clinical examination and mammographic findings indicated malignancy. Histopathological examination showed features of syringomatous adenoma of the nipple. A clinicopathological study and histological differential diagnosis of this unusual tumour is described.     

Ruptured sinus of valsalva presenting late following repair of tetralogy of fallot

Rupture of sinus of valsalva following repair of tetralogy of fallot (TOF) is very rare. It should be suspected as a cause of recurrent or prolonged pleural effusion and congestive cardiac failure in patients who have undergone repair of TOF. We report one such patient.     

Human evolution and tears of the rotator cuff

Purpose

Humans differ from other great ape species in their propensity to develop tears of the rotator cuff. The aim of this study was to compare the anatomical risk factors for subacromial impingement and rotator cuff tears amongst the great apes and to determine which features may be accentuated in humans and therefore play a more significant role in disease aetiology.

Methods

Orthogonal digital photographs of 22 human, 17 gorilla, 13 chimpanzee and 12 orangutan dry bone scapula specimens oriented in the glenoid plane were taken. Anatomical measurements were preformed using a calibrated digital image technique and the results scaled according to scapula vertebral border length.

Results

Of the ten anatomical features associated with subacromial impingement and rotator cuff tears in humans, none were shown to be accentuated and significantly different to the other species studied. However the human supraspinatus fossa was shown to be significantly smaller.

Conclusions

These results indicate that an alternative primary aetiological factor for rotator cuff tears must exist. A reduction in the size of the supraspinatus fossa in human scapulae suggests that structural insufficiency of the supraspinatus or a change in rotator cuff force vectors could play a role.     

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction,apoptosis and inflammation in rats: Possible mechanism of nephroprotection

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney.     

Development of Vorinostat-Loaded Solid Lipid Nanoparticles to Enhance Pharmacokinetics and Efficacy against Multidrug-Resistant Cancer Cells

Purpose

To investigate whether delivery of a histone deacetylase inhibitor, vorinostat (VOR), by using solid lipid nanoparticles (SLNs) enhanced its bioavailability and effects on multidrug-resistant cancer cells.

Methods

VOR-loaded SLNs (VOR-SLNs) were prepared by hot homogenization using an emulsification-sonication technique, and the formulation parameters were optimized. The cytotoxicity of the optimized formulation was evaluated in cancer cell lines (MCF-7, A549, and MDA-MB-231), and pharmacokinetic parameters were examined following oral and intravenous (IV) administration to rats.

Results

VOR-SLNs were spherical, with a narrowly distributed average size of ~100 nm, and were physically stable for 3 months. Drug release showed a typical bi-phasic pattern in vitro, and was independent of pH. VOR-SLNs were more cytotoxic than the free drug in both sensitive (MCF-7 and A549) and resistant (MDA-MB-231) cancer cells. Importantly, SLN formulations showed prominent cytotoxicity in MDA-MB-231 cells at low doses, suggesting an ability to effectively counter the P-glycoprotein-related drug efflux pumps. Pharmacokinetic studies clearly demonstrated that VOR-SLNs markedly improved VOR plasma circulation time and decreased its elimination rate constant. The areas under the VOR concentration-time curve produced by oral and IV administration of VOR-SLNs were significantly greater than those produced by free drug administration. These in vivo results clearly highlighted the remarkable potential of SLNs to augment the bioavailability of VOR.

Conclusions

VOR-SLNs successfully enhanced the oral bioavailability, circulation half-life, and chemotherapeutic potential of VOR.