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Biomedical subjects

M Venkatesh

Publications and source records attributed to M Venkatesh.

11 recordsLinked to original sources

Bioevaluation of radioactive bandages in a murine model of melanoma.

PURPOSE: To study the effectiveness of a radioactive bandage incorporating a beta(-) emitter for the treatment of superficial tumours like melanoma. MATERIALS AND METHODS: (188)Re tin particles were immobilized on a bandage patch ((188)Re bandage). The effectiveness of the (188)Re bandage for controlling tumour growth was tested in C57BL/6 mice bearing BL6/FIO melanoma. The effect of the single dose delivered, two-dose treatment and time of contact of bandages on the skin was studied by following tumour size. RESULTS: Tumour growth was delayed significantly in treated animals compared with controls. Complete tumour regression was observed with some doses of radiation. Histology studies and dose-rate calculations were also carried out to evaluate the effectiveness of (188)Re bandages. CONCLUSIONS: Radioactive bandages could be a promising modality for the treatment of skin cancers.

Animals↗

A toxicological evaluation of 2-dimethylaminomethyl-1-phenyl-2-propen-1-one hydrochloride.

2-Dimethylaminomethyl-1-phenyl-2-propen-1-one hydrochloride (3) is a novel cytotoxic and anticancer agent. The objective of this study was to obtain information pertaining to possible toxic symptoms detected by in vivo evaluations in mice and an in vitro test for mutagenicity. The data obtained revealed that 3 had no effect on alanine transaminase, aspartate transaminase, HDL cholesterol and protein concentrations in sera nor were variations in the numbers of red and white blood cells detected. Furthermore autopsies of treated mice revealed no pathological symptoms in the heart, kidney, brain, spleen and testes. However elevation of the concentrations of total cholesterol, triglycerides, creatinine and urea were noted in treated mice as well as inflammation of the liver and lungs. Chromosomal aberrations were detected in a micronuclei test. In the Ames test, compound 3 was converted into one or more mutagens in the presence (but not the absence) of a murine liver homogenate. Thus future molecular modifications of 3 should bear in mind approaches to reduce or minimize unwanted side effects.

Animals↗

177Lu labelled polyaminophosphonates as potential agents for bone pain palliation.

Polyphosphonate ligands labelled with radioisotopes decaying by moderate energy beta emission have shown utility as palliative agents for painful bone metastasis. 177Lu (T(1/2)=6.71 d, Ebetamax=497 keV) has radionuclidic properties suitable for use in palliative therapy of bone metastasis. 177Lu was produced at a high specific activity and excellent radionuclidic purity by thermal neutron bombardment of a target prepared from natural Lu. Three polyaminomethylene phosphonate ligands, abbreviated as EDTMP, DTPMP and TTHMP, were synthesized and radiolabelled with 177Lu. Complexation parameters were optimized to achieve maximum yields (97-99.5%). All the complexes were found to retain their stability at room temperature even 14 days after preparation. Biodistribution studies of the complexes were carried out in Wistar rats. All the complexes showed significant bone uptake (6-6.5%/g in tibia at 3 h post-injection (p.i.)) with rapid clearance from blood and minimum uptake in soft tissues. These studies reveal that 177Lu complexes with the synthesized ligands have a potential use in palliative treatment of painful bone metastasis.

Animals↗

Preparation and evaluation of 90 Y skin patches for therapy of superficial tumours in mice.

90Y, a beta emitting radionuclide, was immobilized in a bandage patch for possible application for the therapy of superficial maladies such as tumours and skin cancers. The aim was to prepare a radiation source that could deliver uniform dose within a short duration and avoid the inconveniences faced with the gamma sources used in teletherapy and brachytherapy. 90Y-ferric hydroxide macroaggregates were prepared, filtered and immobilized between two layers of gauze. When placed in saline, no radioactivity leached for 3 days, proving its safety for external application. Fibrosarcoma was induced in mice for checking the efficacy of 90Y patches. 90Y patches of various activities were prepared and applied on the tumours. The effect of time gap between inception and treatment of tumour, dose delivered and multiple application in fractionated doses was studied. In all the cases, tumour growth in the treated animals was considerably reduced in comparison with controls. It was concluded from the experiments that treatment should be started at the earliest stage possible, i.e. when the tumour is palpable. Delivery of dose from radioactive patches of approximately 90-100 MBq each, thrice at weekly intervals proved to be more effective for regression of tumour growth.

Animals↗

Optimization and performance evaluation of peptide-loaded monolithic poly-epsilon-caprolactone microspheres in mice bearing melanoma B16F1.

The objective of this investigation was to develop a bleomycin depot based on monolithic microparticulate technology to suppress tumour growth and to maintain constant plasma drug concentrations within an optimal therapeutic window over a prolonged period of time. Formulations were optimized with biodegradable poly-epsilon-carpolactone and evaluated in vitro for physicochemical characteristics, drug release in phosphate buffered saline (pH 7.4) and evaluated in vivo in tumour bearing mice. This investigation revealed that upon subcutaneous injection, the biodegradable depot-forming poly-epsilon-carpolactone microspheres controlled drug release and suppressed tumour growth kinetics significantly compared to control. A preliminary pharmacokinetic evaluation exhibited steady plasma drug concentrations during the study period. This formulation with its reduced frequency of administration and better control of drug disposition is expected to provide an economic benefit to the user compared with products currently available for chemotherapy.

Animals↗

A slotted waveguide applicator for continuous flow grain drying.

A slotted waveguide antenna was designed and developed with series slots cut on the broad side that constituted a popular means of coupling microwaves with grain for drying. The radiating characteristics of the slotted wave guide antenna mounted in a setup that simulated the coupling to a grain conveying tube were studied at a frequency of 2.45 GHz. The antenna consisted of a WR-340 waveguide made of copper. The effect of the slot inclination angle O, moisture content and the shape of the slots were investigated. The results indicated 55 degrees as an optimum slot angle for slots having a width of 13 mm and a length 58 mm. Slots with a width of 6 mm did not exhibit any regular behavior and the effect of O was not clearly identified.

Desiccation↗

A novel [186/188Re]-labelled porphyrin for targeted radiotherapy.

The concept of labelling a porphyrin, a tumour-avid agent, with a radionuclide to evaluate its potential as a therapeutic modality is reported. A novel water-soluble porphyrin, namely meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]porphyrin, with suitable dicarboxylic acid groups as aromatic substituents in the periphery, was synthesized and characterized. The labelling of this porphyrin with 186/188Re, a beta(-) emitter, was optimized by varying the reaction conditions. The complexation yield was >98% as estimated by paper chromatography in acetone and in saline. The radiochemical purity was found to remain at >98% when stored at 4 degrees C for 24 h. Biodistribution studies in Swiss mice bearing fibrosarcomas showed an uptake of approximately 3.5% per gram of tumour at 30 min post-injection. This uptake in the tumour was retained until 24 h post-injection with major activity showing renal clearance; no significant activity was present in other organs of interest. The tumour/blood and tumour/muscle ratios were observed to be 38 and 5, respectively, at 24 h post-injection, thereby indicating a possible therapeutic potential for tumours.

Animals↗

Radiolabelled monoclonal antibodies against human cardiac myosin.

Myocardial infarction (MI) can be monitored using several protein markers including human cardiac myosin (HCM). Monoclonal antibodies were raised against HCM by hybridoma technique. Antimyosin antibody producing clones were identified by ELISA and monoclonality was established by limiting dilution. The antibodies were purified, isotyped and their cross reactions with myosin from other species were estimated. All the clones showed negligible cross reaction with rabbit myosin, but reacted with bovine skeletal myosin to different extents (40-100%). The most avid antibody Mab 4G4 which also strongly reacted with rat cardiac myosin, was labelled with 125I using different oxidising agents such as iodogen, chloramine-T and lactoperoxidase. More than 95% pure radiolabelled antibody could be obtained by gel filtration. The immunoreactivity was retained. Mab 4G4 was also labelled with 99mTc using stannous tartrate as the reducing agent. Radiolabelling yield was approximately 60%, the purity was >95%. Both the radiolabelled preparations were tested for biodistribution in rats--both normal and those with induced MI. Approximately 0.7 % of the injected activity/g was found in the infarcted region and the accumulation of activity in the infarcted heart was 1.5 times that in the normal heart. A very high percentage of activity (80%) accumulated in the thyroid. With further optimisation of labelling and use of F(ab')2 fragments, better delineation of the infarct sites may become possible.

Animals↗

An Rh-105 complex of tetrathiacyclohexadecane diol with potential for formulating bifunctional chelates.

1,5,9,13-Tetrathiacyclohexane-3,11-diol (16S4-diol), a sulfur crown ether analog, was studied as a potential chelating agent to complex no-carrier-added (NCA) grade 105Rh(III) in high yield at low ligand concentrations. trans-[RhCl2(16S4-diol)]chi (chi = Cl, PF6) was prepared using nonradioactive RhCl3.3H2O and characterized by UV-Vis, nuclear magnetic resonance (NMR) and X-ray crystallography. It was shown to have a +1 charge with the Rh(III) metal center coordinated to the four S atoms equatorially and two Cl atoms in trans axial positions. The 105Rh-16S4-diol complex prepared with NCA 105Rh(III)-chloride reagent was found to exhibit identical chromatographic properties as trans-[Rh(III)Cl2(16S4-diol)]+ (including silica and C-18 thin-layer chromatography [TLC] and electrophoresis). The preparation of 105Rh-16S4-diol complex formation optimized for conditions of pH, temperature, time, % ethanol and quantity of 16S4-diol resulted in yields > 90%. Very low quantities of 16S4-diol (3 nmol) complex NCA 105Rh(III) under relatively mild reaction conditions (heating at 64 degrees C for 90 min) in the presence of ethanol (10%), yielded the high specific activity 105Rh-16S4-diol complex as a single cationic species. The 105Rh-16S4-diol complex was shown to be stable for > or = 4 days in physiological buffers at room temperature and in human serum at 37 degrees C.

Chelating Agents↗

Acute appendicitis mistaken as acute rejection in renal transplant recipients.

Case histories of 2 renal transplant recipients are reported who had presenting features of fever, leukocytosis and pain/tenderness over right iliac fossa and were diagnosed to be due to acute appendicitis rather than more commonly suspected acute rejection episode which has very similar features. Diagnosis of acute appendicitis was suspected on the basis of rectal examination and later confirmed by laparotomy. The purpose of this communication is to emphasize the need for proper diagnosis in patient with such presentation; otherwise wrong treatment may be received.

Acute Disease↗