Enzymatic degradation study of 111In-labeled minigastrin peptides using cathepsin B enzyme and AR42J cancer cell line for the development of neuroendocrine tumor imaging radiopharmaceuticals

Neuroendocrine tumors [NET] are the rare tumors which often impose graveyard threat. These tumors are characterized by the overexpression of various G-protein coupled receptors including cholecystokinin [CCK] receptors-1 and 2 [A or B]. Minigastrin peptides are being investigated for theranostic purposes of CCK-2 receptor positive NET. The minigastrin analogue [APHO70] was modified by engineering enzyme susceptible tetrapeptide sequence into APHO70 peptide to reduce the random degradation by lysosome enzymes which pave the way to random trafficking in patient's body and dipeptide addition at c-terminus. All the four modified minigastrin peptides [MG-CL1-4] were investigated for lysosome cathepsin B [catB] enzyme susceptibility and fate into AR42J cancer cell line. The indium-111 labeled MG-CL1-4 peptides were also studied for target [tumor] and non-target saccumulation by using tumor induced mice. The RP-HPLC analysis result showed nonspecific cleavage of standard 111In-APH070 and 111In-MGCL1 while specific cleavage was noted in case of 111In-MGCL [2-4]. The effect of specific and non-specific cleavage on biodistribution in tumor induced nude mice model indicates the promising accumulation of 111In-MGCL2, 111In-MGCL3, and 111In-MGCL4 radiotracers while 111In-MGCL1 showed less accumulation. 111In-MGCL2 and 111In-MGCL3 showed highest target-to-kidney ratio [T/K] i.e. 1.71 and 1.72, respectively whereas standard compound showed T/K 1.13. In conclusion, the two indium-111 labeled analogues i.e. 111In-MGCL2 and 111In-MGCL3 showed promising sensitivity for tumor and could be tested for further investigation to reach pre-clinical studies

Radiolabeling of benzylpenicillin with lutetium-177: quality control and biodistribution study to develop theranostic infection imaging agent

Benzylpenicillin acts through binding with beta-lactamase enzyme and inhibiting the bacterial cell wall biosynthesis. Therefore, the radiolabeling of benzylpenicillin with lutetium-177 is expected to serve as a theranostic agent for deep-seated bacterial infections. The radiolabeling of benzylpenicillin resulted tilde 93% radiochemical yield at optimized reaction conditions. Radiochemical purity analysis was tested with the help of Whatman No. 2 paper and instant thin layer chromatography. Biodistribution study with healthy New Zeeland white rabbit revealed moderate accumulation in different organs. Kidneys are the major organs, showed not more than 4.57+/-0.89% injected dose per gram organ [ID/gm organ] at 1 h time point and 3.48+/-1.11% ID/gm organ at 6 h time point. The accumulation of tracer agent in liver was found in the range of 7.42+/-2.42% to 9.09+/-2.76 ID/gm organ. The glomerular filtration rate studies revealed rapid clearance - omitting the chance of nephrotoxicity. The radiolabeling yield, biodistribution and glomerular filtration rate results revealed [177]Lu-benzylpencillin could be a potential candidate to diagnose the deep-seated bacterial infection

Antioxidant, antibacterial and antiproliferative activities of pumpkin (cucurbit) peel and puree extracts - an in vitro study

Natural resources right from the beginning of the human civilization has paved the way to human being to combat different challenges. The big challenge was to safe the human being from diseases and shortage of food. Plants helped the man in both areas very efficiently. No doubt when plants are used as food actually we are also taking lot of compounds of medicinal values in an excellent combination which naturally reduce the risk of diseases. Extraction and purification of several medicinally important compounds also gave the way to develop pharmaceutical industry in addition to its own therapeutic effects against different lethal diseases. Pumpkin is one of the several medicinal important vegetables used in different way on the behalf of its admirable power to combat different diseases. Antioxidant and biological studies showed very important results. A good coherence was found among extraction yield [10.52 to 18.45%], total phenolics [1.13 to 6.78 mg GAE/l00g], total flavonoids [0.23 to 0.72mg CE/l00g] and antioxidant potential [-70%]. Antibacterial assays of peel and puree extracts advocated good potential to stop the growth and division of pathogenic bacteria. Further biological activity study was carried out using MDBK cancer cell line. The growth inhibitory effect on cancer cell line using MTT assay showed methanol extracts of peel and puree both remained efficient to inhibit growth [-35%] and cell division of cancer cells. Our results showed that extracts of pumpkin puree and its waste, peel, may be utilize to prepare functional food against pathogenic born diseases and most active compounds may also be extracted, concentrated and converted into tablets or suspension form for therapeutic purposes

Antioxidant and antibacterial activities of Hibiscus Rosa-sinensis Linn flower extracts

Antioxidant and antibacterial potential of different solvent extracts of locally grown Hibiscus rosa-sinensis Linn was evaluated. The antioxidant activity was assessed by estimation of total flavonoids contents, total phenolic contents, DPPH free radical scavenging activity and percentage inhibition of linoleic acid oxidation capacity. Agar disc diffusion method was used to assess antibacterial potential of crude extract of H. rosa-sinensis. The yield of the crude extracts [23.21 +/- 3.67 and 18.36 +/- 2.98% in 80% methanol and ethanol solvents was calculated, respectively. Methanol and ethanol extract of H. rosa-sinensis showed total phenolics 61.45 +/- 3.23 and 59.31 +/- 4.31 mg/100g as gallic acid equivalent, total flavonoids 53.28 +/- 1.93 and 32.25 +/- 1.21 mg/100g as catechine equivalent, DPPH free radical scavenging activity 75.46 +/- 4.67 and 64.98 +/- 2.11% and inhibition of linoleic acid oxidation potential 75.8 +/- 3.22 and 61.6 +/- 2.01% respectively, was measured. Antibacterial study against three human pathogens such as staphlococus sp. Bacillus sp. and Escherichia coli showed growth inhibitory effect in the range of 12.75 +/- 1.17 to 16.75 +/- 2.10 mm. These results showed H. rosasinensis indigenous to Kallar Kahar and its allied areas bear promising medicinal values and could be used for developing herbal medicines to target oxidative stress and infectious diseases.

Undetected hypothyroidism and its anesthetic implications

Hypothyroidism is a common disorder affecting the cardiovascular, respiratory, hematopoietic, and renal organ systems. Each of these systems is particularly relevant in the management of the surgical patient. Most reported complications have occurred in patients with unrecognized hypothyroidism. In general, treatment of recognized hypothyroidism is recommended before any surgical procedure whenever possible and normal levels of thyroid hormone should be documented as part of the preoperative evaluation. Such a strategy is likely to result in better surgical outcomes with improved morbidity and mortality