Targeting of somatostatin receptors expressed in blood cells using quantum dots coated with vapreotide.

Cancer may be difficult to target, however, if cancer targeted this provides the chance for a better and more effective treatment. Quantum dots (Qdots) coated vapreotide (VAP) as a somatostatin receptors (SSTRs) agonist can be efficient targeting issue since may reduce side effects and increase drug delivery to the target tissue. This study highlights the active targeting of cancer cells by cells imaging with improving the therapeutic outcomes. VAP was conjugated to Qdots using amine-to-sulfhydryl crosslinker. The synthesized Qdots-VAP was characterized by determination of size, measuring the zeta-potential and UV fluorometer. The cellular uptake was studied using different cell lines. Finally, the Qdots-VAP was injected into a rat model. The results showed a size of 479.8 ±â€¯15 and 604.88 ±â€¯17 nm for unmodified Qdots and Qdots-VAP respectively, while the zeta potential of particles went from negative to positive charge which proved the conjugation of VAP to Qdots. The fluorometer recorded a redshift for Qdots-VAP compared with unmodified Qdots. Moreover, cellular uptake exhibited high specific binding with cells which express SSTRs using confocal microscopy and flow cytometry (17.3 MFU comparing to 3.1 MFU of control, P < 0.001). Finally, an in vivo study showed a strong accumulation of Qdots-VAP in the blood cells (70%). In conclusion, Qdots-VAP can play a crucial role in cancer diagnosis and treatment of blood cells diseases when conjugated with VAP as SSTRs agonist.

Perindopril regulates the inflammatory mediators, NF-κB/TNF-α/IL-6, and apoptosis in cisplatin-induced renal dysfunction.

Cisplatin (CP) is an essential chemotherapeutic drug used over the world against many types of cancer. It has several side effects such as ototoxicity, myelosuppression, and nephrotoxicity. Nephrotoxicity is the most dangerous and is considered a dose-limiting one. Oxidative stress, inflammation, and apoptosis are involved in this toxicity. This study was conducted to focus on the impact of perindopril (PER) against CP-induced nephrotoxicity in rat. Male albino rats were divided to control, rats received a single dose of CP, rats received PER, and rats co-received PER and CP. Nephrotoxicity evoked by CP challenge was characterized histologically and biochemically including significant increase in relative kidney/body weight ratio and serum urea and creatinine. Additionally, CP markedly increased renal tissue content of malondialdehyde (MDA) while decreased reduced glutathione (GSH) and depleted glutathione-S-transferase (GST) activity. CP produced significant increase in the inflammation biomarkers; nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interlukine-6 (IL-6). Administration of CP clearly upregulated caspase-3, while it downregulated B-cell lymphoma-2 (BCL-2) gene expressions. Perindopril treatment showed a significant restoration in the pathological alterations histologically and biochemically, which are provoked by CP administration. Altogether, these results suggested a good therapeutic role of PER against CP-induced nephrotoxicity through its influence on oxidative stress, inflammation, and apoptosis pathway.

Neural and Endocrinal Pathobiochemistry of Vitiligo: Comparative Study for a Hypothesized Mechanism.

The etiology of vitiligo is still unclear. The aim is to investigate a neural and hormonal etio-pathology of vitiligo. Sixty acrofacial vitiligo patients were divided into two subgroups as active vitiligo patients group (AVPs; n = 35) and stable vitiligo patients group (SVP; n = 25). Forty healthy subjects without any systemic or dermatological disease were used as controls. Blood samples were collected, and the samples were used for measurement of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), cortisol, estrogen, testosterone, melatonin, and prolactin levels by ELISA, while norepinephrine (NE), epinephrine (Epi), dopamine (DA), homo-vanillic acid (HVA), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) by high-pressure liquid chromatography. The current results showed a significant increase in plasma levels of Epi, NE, DA, HVA, serotonin, 5-HIAA, melatonin, and in serum level of TSH and prolactin either in SVP or AVP groups than the control group and in AVP than SVP group. The serum levels of fT3 and fT4 were significantly decreased either in SVP or AVP groups than the control group. A significant increase in estradiol levels was observed in females within AVP than females in either SVP or control groups. There was a significant increase in serum level of cortisol in AVP than either SVP or control group. There was a significant decrease in serum level of ACTH in either AVP or SVP than control and in AVP than SVP group. In conclusion, there are some neural and endocrine markers that play a pivotal role in pathogenesis and/or consequences of vitiligo. The abnormally disturbed levels of theses markers lead to melanocyte destruction and/or depigmentation.

Curcumin ameliorate DENA-induced HCC via modulating TGF-ß, AKT, and caspase-3 expression in experimental rat model.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. In laboratory animal models, diethylnitrosamine (DENA) is a well-known agent that has a potent hepatocarcinogenic effect that is used to induce HCC. As curcumin has a potent anti-inflammatory effect with strong therapeutic potential against a variety of cancers, our present study aims to investigate its curative effects and the possible mechanisms of action against DENA-induced HCC in male rats. Investigation of biochemical and molecular parameters of HCC animal model liver showed an overexpression of TGF-ß and Akt proteins accompanied with a significant reduction of the proapoptotic marker caspase-3. DENA-induced hepatic cellular injury resulted also in a significant increase in liver function marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid peroxides in this group. Curcumin treatment partially reversed DENA-induced damage as it reduced the overexpression of the angiogenic and anti-apoptotic factors TGF-ß and Akt and improved caspase-3 expression. Also, it could partially normalize the serum values of liver marker enzymes and lipid peroxidation and improve liver architecture. Curcumin shows a unique chemotherapeutic effect in reversing DENA-induced HCC in rat model. This effect is possibly mediated through its proapoptotic, antioxidant, anti-angiogenic, as well as antimitotic effects. It interferes and modulates cell signaling pathways and hence turns death signals and apoptosis on within tumor cells.

Behavior of intraocular pressure after intravitreal injection of triamcinolone acetonide among egyptians.

PURPOSE: To evaluate the changes in intraocular pressure (IOP) after intravitreal injection of triamcinolone acetonide for the management of diabetic macular edema (DME). METHODS: The study design is a prospective, interventional, two-arm, dose-response study. Nineteen patients with bilateral DME were included, one eye for every patient underwent intravitreal injection of 4 mg triamcinolone acetonide (group A, 19 eyes), and the other eye of the same patient underwent intravitreal injection of 8 mg triamcinolone acetonide (group B, 19 eyes); the selection as to which eye was to receive either dose was random. The patients were followed up for 6 months after injection; complete ophthalmological examination and optical coherent topography were done. RESULTS: Intravitreal triamcinolone acetonide was effective in reduction of DME in group A in the first 3 months only, while in group B with high dose (8 mg) the improvement continued for 6 months after injection. Significant IOP rise was observed in both groups with an incidence of 68.1% and 73.7% in groups A and B, respectively. IOP-lowering drugs were used to control IOP; however, one patient in each group needed glaucoma filtration surgery in both eyes after intractable glaucoma with failure of medical treatment. CONCLUSION: Although intravitreal injection of triamcinolone acetonide is very effective in managing DME and with lower cost than other modalities, the rise in IOP and the burden of glaucoma are major concerns. High corticosteroid responder is an individualized reaction irrespective of the intravitreal triamcinolone acetonide dose used.