Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

Nephrotoxic effects of Valeriana wallichii

Aminoglycosides are the commonly used antibiotics against Gram negative bacteria. Their clinical applications are limited due to nephrotoxic side effects. Therefore, the current study was undertaken in an attempt to increase the use of these drugs without causing nephrotoxicity by exploring the nephroprotective effects of a medicinal plant with high flavonoid contents and strong antioxidant properties, namely Valeriana wallichii. A daily dose of 200mg/kg of the extract derived from V. wallichii was employed for a period of three weeks. The results obtained revealed that co-therapy of extract with gentamicin protected some changes in renal functions; however, failed to provide a complete protection as assessed by biochemical, physiological and histological parameters. It can be concluded from the current findings that V. wallichii failed to deliver protective effects against gentamicin induced renal damage in spite of strong flavonoid contents and antioxidant properties

Nephroprotective property of Cinnamomum zeylanicum and its antibacterial activity in combination with gantamicin

Cinnamomum zeylanicum has strong antioxidant properties and has been presented to have nephroprotective effects. Present work was aimed to study the nephroprotective property of the plant extract through urinary enzymes excretion, to confirm its protective effects and to observe the antibacterial activities of gentamicin in combination with the plant extract. 200mg/kg/day of the plant extracts were administered alone and as co-therapy with gentamicin. Urinary lactate dehydrogenase [LDH] and Urinary alkaline phospatase [ALP] excretions were observed through reagents kits with the help of Power-Lab 300. Antibacterial activities were assessed for gentamicin alone and in combination with the extract. Present study showed that the plant extract have excess quantity of flavonoids, which may responsible for attenuating the excessive excretion of urinary LDH. However, Urinary ALP excretion was found remained same throughout the study period in all experimental groups; might be detected in acute damage. Further, the plant also proved to have no decreasing impact on the antibacterial activities of gentamicin

Nephroprotective potentials of Citrus aurantium: a prospective pharmacological study on experimental models

Citrus aurantium is traditionally used in various kidney problems like burning of urine, urinary hesitancy and renal colic. The main objective of the present work was to evaluate the protective role of Citrus aurantium against gentamicin induced renal damage, due to its free radical scavenging properties to present experimental facts for their traditional use. 200 mg/kg/day of ethanolic extract of the plant employed in combination with the toxic doses of gentamicin for twenty-one days. The group GC-au [animals treated with co-administration of Citrus aurantium and gentamicin] protected renal damage expected with gentamicin, assessed by known functional and morphological parameters, significantly different from group G [animals treated with gentamicin]. All the renal functioning parameters including; Blood urea nitrogen, Serum creatinine, Serum uric acid, Creatinine clearance, Serum electrolytes, Body weight, Urinary volume, Enzyme excretions, Urinary protein excretions and histological examination was performed for each and every group animals. The plant extract proved to have nephroprotective potentials may because of its known flavonoid contents and antioxidant properties.

Outcome of primary percutaneous coronary intervention [PCI] of ostial versus nonostial occlusion of left anterior descending artery [Study conducted at National Institute of Cardiovascular Diseases, Karachi]

Object: The object of this study was to compare the outcome of primary PCI of ostial versus non ostial occlusion of LAD artery

Materials and Methods: This observational study was conducted at National Institute of Cardivascular Diseases Karachi, Pakistan from January 1[st], 2008 to December 31[st], 2008. A total of 70 patients presented to the catheterization laboratory for primary PCI of LAD artery in whom baseline coronary angiogram showed acute occlusion of left anterior descending artery were enrolled for the study. All patients received Aspirin, Clopidogrel and Platelet Glycoprotein IIB IIIA inhibitor. Patients were followed at one month, 3 months and 6 months

Results: Out of 70 cases 50 had nonostial and 20 had ostial occlusion. Baseline characteristics were similar between both groups. Stenting was done in 95% of all patients and was similar in patients with ostial or nonostial narrowing. Procedural success was the same for ostial and nonostial Primary PCI [100% vs. 96%]. Six months event free survival was also similar in both groups [75% vs. 76%]. Total event rate and mortality was also same in both groups [25% vs. 24% and 10% vs. 10%]

Conclusion: Primary PCI of ostial LAD occlusion with suitable anatomy is as safe and similar as non ostial LAD occlusion and optimal results can be achieved in this high risk group of patients in a developing country at a tertiary care public sector hospital. To validate our results further studies with larger cohort are needed

Effect of lemon grass and green tea on blood pressure and heart rate

Lemon grass and Green tea are the herbal products, widely used, next to that of water. Because of their common use, it is so much necessary to find their effects on all the body functions. In the current study its effects of blood pressure and heart rate of human male has been evaluated. Observational study. This study was conducted at Pharmacy Department, University of Malakand. Seventy two male volunteers for each tea had been selected and the blood pressure before and after giving one cup of each tea to each individual was evaluated by using sphygmomanometer and stethoscope. A minor increase in blood pressure was noted in the volunteers taken green tea. On other hand a moderate decrease in the systolic blood pressure and mild increase in the diastolic blood pressure were noted in the case of lemon grass. Also, great decreases in the heart rate of individuals taken lemon grass, and a moderate increase in the heart rate of individuals taken green tea were observed. From the current study it can be concluded that the Male heart patients are on the high risk to the use of either type of tea, so they have to take care while using either type of tea in excess quantity

Effect of decoction of camellia sinensis on blood pressure and heart rate

Camellia sinensis as a tea [hot decoction] is so widely used throughout the Asia. Therefore to find out, their effects on all the body functions are the need of hour. In the current study the effect of Camellia sinensis on human [females] blood pressure has been evaluated. Observational study. This study was conducted at Pharmacy Department, University of Malakand. The blood pressure before and after giving the decoction of Camellia sinensis to seventy six individuals was evaluated by using sphygmomanometer and stethoscope. A moderate increase in the blood pressure had been noted. Also a great decrease in the heart rate of individuals has been identified after taking the decoction. From the current study it can be concluded that green tea have an effect of increasing blood pressure in the females, so the heart patients have to take care while using green tea in excess quantity

CNS stimulant activity of Qurs saffron [a herbal medicine] in experimental animal models

To confirm the safety and efficacy of the product for human health due to its wide use and to explore its effects on CNS. Experimental and observational. This study was conducted at Frontier medical college Abbottabad Pakistan in March 2011. Thirty rabbits divided into five groups were administered Qurs saffron at the dose of 50, 100 and 200 mg/kg, Caffeine 100mg/kg orally and the last group was taken as control group, received normosaline. The animals were observed for behavioral changes at 30 min intervals. At 50mg/kg of the drug were found to have mild stimulant activity, while 100mg/kg were found to have a moderate CNS stimulant properties same like caffeine at a dose of 50mg/kg. While at a dose of 200mg/kg_Qurs saffron were found to have a strong stimulant properties. From the current study it can be concluded that the product have dose dependent CNS stimulant effects