Induction of Mitochondrial Cell Death and Reversal of Anticancer Drug Resistance via Nanocarriers Composed of a Triphenylphosphonium Derivative of Tocopheryl Polyethylene Glycol Succinate.

We have devised a nanocarrier using "tocopheryl polyethylene glycol succinate (TPGS) conjugated to triphenylphosphonium cation" (TPP-TPGS) for improving the efficacy of doxorubicin hydrochloride (DOX). Triphenylphosphonium cation (TPP) has affinity for an elevated transmembrane potential gradient (mitochondrial), which is usually high in cancer cells. Consequently, when tested in molecular docking and cytotoxicity assays, TPP-TPGS, owing to its structural similarity to mitochondrially directed anticancer compounds of the "tocopheryl succinate" family, interferes specifically in mitochondrial CII enzyme activity, increases intracellular oxidative stress, and induces apoptosis in breast cancer cells. DOX loaded nanocarrier (DTPP-TPGS) constructed using TPP-TPGS was positively charged, spherical in shape, sized below 100 nm, and had its drug content distributed evenly. DTPP-TPGS offers greater intracellular drug delivery due to its rapid endocytosis and subsequent endosomal escape. DTPP-TPGS also efficiently inhibits efflux transporter P glycoprotein (PgP), which, along with greater cell uptake and inherent cytotoxic activity of the construction material (TPP-TPGS), cumulatively results in 3-fold increment in anticancer activity of DOX in resistant breast cancer cells as well as greater induction of necroapoptosis and arrest in all phases of the cell cycle. DTPP-TPGS after intravenous administration in Balb/C mice with breast cancer accumulates preferentially in tumor tissue, which produces significantly greater antitumor activity when compared to DOX solution. Toxicity evaluation was also performed to confirm the safety of this formulation. Overall TPP-TPGS is a promising candidate for delivery of DOX.

Click Biotinylation of PLGA Template for Biotin Receptor Oriented Delivery of Doxorubicin Hydrochloride in 4T1 Cell-Induced Breast Cancer.

PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However, adequate entrapment of a hydrophilic bioactive like DOX in a hydrophobic polymer system made of PLGA is not usually possible. We therefore modified a conventional W/O/W emulsion method by utilizing NH4Cl in the external phase to constrain DOX in dissolved polymer phase by suppressing DOX's inherent aqueous solubility as per common ion effect. This resulted in over 8-fold enhancement in entrapment efficiency of DOX inside BPNP, which otherwise is highly susceptible to leakage due to its relatively high aqueous solubility. TEM and DLS established BPNP to be sized below 100 nm, storage stability studies showed that BPNP were stable for one month at 4 °C, and in vitro release suggested significant control in drug release. Extensive in vitro and in vivo studies were conducted to propound anticancer and antiproliferative activity of BPNP. Plasma and tissue distribution study supplemented by pertinent in vivo fluorescence imaging mapped the exact fate of DOX contained inside BPNP once it was administered intravenously. A comparative safety profile via acute toxicity studies in mice was also generated to out rightly establish usefulness of BPNP. Results suggest that BPNP substantially enhance anticancer activity of DOX while simultaneously mitigating its toxic potential due to altered spatial and temporal presentation of drug and consequently deserve further allometric iteration.

A study of dose response and organ susceptibility of copper toxicity in a rat model.

Copper (Cu) in higher concentration is toxic and results in various organ dysfunction. We report Cu concentration in liver, brain and kidney in the rat model following chronic exposure of oral copper sulphate at different subtoxic doses and correlate the tissue Cu concentrations with respective organ dysfunction. Fifty-four male wistar rats divided in 3 groups, the control group received saline water and the experimental group (Group-IIA and IIB) received oral copper sulphate in dose of 100 and 200mg/kg Body Weight. At the end of 30 days, 60 days and 90 days of exposure, six rats were sacrificed from each group. The maximum peak force in grip strength, latency to fall in rotarod and percentage attention score in Y-maze were significantly reduced in the copper sulphate exposed rats compared to the controls at all time points and these were more marked in Group-IIB compared to Group-IIA. Cu concentration was significantly higher in liver, kidney and brain in the Group-II compared to the Group-I. The Cu concentration was highest in the liver (29 folds) followed by kidney (3 folds) and brain (1.5 folds). Serum ALT, AST and bilirubin correlated with liver Cu, BUN with kidney Cu, and grip strength, rotarod and Y-maze findings correlated with brain Cu level. In rats, chronic oral copper sulphate exposure at subtoxic level results in neurobehavioral abnormality and liver and kidney dysfunctions due to increased Cu concentration in the respective organs. Liver is the most vulnerable organ and copper toxicity increases with increasing dose and duration of exposure.

Foreign body in ENT--general practitioner's duty.

Foreign body in ENT region is an age-old problem. Introduction of foreign body in ear, nose and throat is specially seen in children. There are many types of foreign body seen in the ear, nose and throat. They can aspirate into larynx, trachea and bronchus. How to manage the removal of foreign body in ear, nose and throat had been discussed in a nutshell. General practitioners should be skilled enough to remove foreign body with their limited resources and they should know when to send the cases to an ENT specialist or to a hospital.

Cellular immune responses to recombinant Plasmodium vivax tryptophan-rich antigen (PvTRAg) among individuals exposed to vivax malaria.

Plasmodium vivax, the most widespread species of human malaria parasite responsible for 70-80 million cases each year requires a vaccine. In recent years, many potential vaccine candidate antigens have been identified from P. vivax including PvTRAg. We describe here cellular immune response to recombinant PvTRAg expressed in Escherichia coli. The in vitro stimulation of PBMCs derived from P. vivax-exposed individuals (n = 16) showed strong proliferative response (SI > 2.2) to PvTRAg as compared to PBMCs from normal healthy controls (n = 8). Although both Th1 (IFN-gamma, TNF-alpha and IL-12) and Th2 (IL-4 and IL-10) cytokines were secreted by the PBMCs of the P. vivax-exposed individuals in response to PvTRAg, the overall response was more inclined towards Th2. In conclusion, recombinant PvTRAg was found to elicit strong cellular immune response among the P. vivax-exposed individuals.

The effect of vitamin E on acute skin reaction caused by radiotherapy.

Ionizing radiation affects healthy organs and tissues as well as diseased tissues during radiation therapy. Skin reactions varying from acute erythema to necrosis can be seen. It has been found that vitamin E can prevent mutagenic and/or carcinogenic effects of ionizing radiation in both animals and cell cultures. This study investigated the preventative effect of antioxidant vitamin E on irradiation-induced acute skin reactions. No protective effect of vitamin E was demonstrated. It is possible that the vehicle induced free radical exposure in the irradiated skin.

Results of chemoirradiation after curative resection of locally advanced gastric cancer.

To evaluate the results of post-operative chemoirradiation for gastric carcinoma. The records of 58 patients who underwent resection for gastric carcinoma were retrospectively reviewed. Forty-six patients had complete resection without any residual disease but with high-risk factors of relapse. Twelve patients had microscopic residual disease. Doses of irradiation ranged from 45 to 54 Gy with a median dose of 49 Gy in 1.8 Gy fractions. Fifty-three of the patients received 5-fluorouracil-based concomitant chemoradiotherapy, and all of them received chemotherapy after the completion of radiotherapy. The median survival of the entire group of patients was 21 months. The 30th month disease-free and overall survival after surgery was 32 and 45%, respectively. The median survival time and 30th month survival rate was 23 months and 54% in patients with no residual disease, and 15 months and 18% for those with residual disease, respectively (p = 0.049). A statistically significant correlation was detected between residual disease and survival and between high-grade tumour and survival (p < 0.05 for each). Patients with both nodal involvement and direct tumour extension beyond the gastric wall have a high risk of locoregional failure, and adjuvant chemoradiotherapy reduces local failure and improves survival.

A clinical study of nasopharyngeal masses.

Out of 36511 patients attending the ENT OHD of R. G,. Aur Medical Callege & Hospital. Kolkata, in one year 0.08% patients were found tuning naspharyngeal mass. 30 cases of nasopharyngeal mass were studied. The peak incidence of nasopharyngeal mass was in the age group between II to 20 years (40%). The incidence in males (73%) was more than females(27%). The maximum ineldence was found among students (74%). Commonest ntuopharyngeal nuns teas antrochoanal polyp (30%). Next commlon masses were adenoids (23%)Juvenile angwfibroma(20%) and nasophartngeal carcinoma (13%). Nasal obstruction was the main presenting symptom(83%) followed by epistaxis (40%).

Large capillary haemangioma arising from the nasal columella--a case report.

A 39-year-old male presented with a mass arising from the nasal columella for last 8 months. The mass was lobulated, dark red in colour, firm in consistency and approximately 3 cm in diameter. It was attached to the columella of the nose by a narrow stalk. The mass was excised completely under general anaesthesia and histopathological examination suggested it to be a case of capillary haemangioma.

Inhibition of epidural scar tissue formation after spinal surgery: external irradiation vs. spinal membrane application.

PURPOSE: The scar tissue that forms after lumbar dissection is a severe complication and a cause of lumbar and radicular pain. It was recently shown that radiotherapy could inhibit peridural fibrosis after laminectomy. In this study, the efficiency of external irradiation was compared with spinal membrane application. METHOD AND MATERIALS: Thirty male New Zealand rabbits underwent L5 laminectomy. Ten rabbits each received a single fraction of 900-cGy external irradiation administered by 9-MeV electron beam 24 h after the surgery. Ten other rabbits each had spinal membrane applied during laminectomy. The remaining 10 rabbits constituted the control group. All of the rabbits were killed 30 days after the laminectomy. Axial histologic sections through the laminectomy defect were evaluated. Each specimen was scored for the extent and density of fibrosis and arachnoidal adherence. RESULTS: The extent and density of fibrosis and arachnoidal adherence differed significantly between the control group and the treatment groups (p < 0.05). However, the extent and density of fibrosis and arachnoidal adherence did not differ significantly between the spinal membrane and irradiation groups (p > 0.05). CONCLUSION: This preliminary study showed that high-single-fraction/low-total-dose administered postoperatively can successfully inhibit postsurgical epidural fibrosis as effectively as applied spinal membrane.

Bilateral antrochoanal polyps.

An extremely rare case of bilateral antrochoanal polyp in an otherwise fit 12-year-old girl is reported. The antrochoanal polyps were removed by bilateral Caldwell-Luc operation. Histopathological examination showed them to be of benign inflammatory nature.

Microlaryngoscopic study of 100 cases of Hoarseness of voice.

100 patients with hoarseness of voice were studied with the help of microlaryngoscopy along with other conventional methods. The peak incidence of the laryngeal diseases was in the age group between 21 to 30 years (28%). The incidence in males (56%), was more than females (44%). Maximum incidence was found among house-wives (29%). 72% patients had a history of vocal abuse. Commonest disease was vocal nodule (30%). The ratio of unilateral and bilateral affection was near about 5 : 4. Hoarseness of voice due to vocal nodules, Reinke's oedema, vocal polyps or fibroangioma was cured in 88%-100% of the cases by microlaryngeal surgery.

Intracerebral malignant fibrous histiocytoma in a 5-year-old girl.

A case of primary intracerebral malignant fibrous histiocytoma (MFH) in 5-year-old girl is presented, the eighteenth case so described in modern literature. A lobulated, heterogenous mass lesion with a haemorragic component was present in our case' s MRI. A review of the literature on MFH of the pediatric age group was done to establish guidelines for standard treatment modalities in primary intracerebral MFH.

Foreign bodies in the larynx.

Inhalation of foreign body is a serious event. A very small proportion of foreign bodies get impacted in the larnyx. Any [foreign body in the larynx presents usually as a respiratory (emergency, when urgent recognition is required to prevent disaster. Two cases of fish bone impacted in the larynx, one in anteroposterior and another in coronal disposition are presented here along with a brief review of literature.

Play safe with safety pins.

Three cases of Safety pins in the aerodigestive tract have been presented here with a brief review of litereture.

An arrow in the nasal cavity, ethmoid and nasopharynx.

A penetrating foreign body (Metallic arrow) involving the ethmoidal air cells nose and nasopharynx is being reported.

Edibe plants of shan tribe of assam.

The Paper presents an accounts of wild edible food plants used by shan tribe of Assam. The shan tribe of Assam is Sino-Tibetan race of Mongoloid stock whose ancestors migrated from South -west china. They depend upon forest products for their day to day needs, i.e, food, fodder and shelter etc. Their food include leaves, tubers, bulbs, rhizomes, flowers fruits and seeds of various wild plants species which they collect from the forest. The present study was conducted during the year 1991-94 in Golaghat, Karbi-Anglong, Lakhimpur, Dibrugarh and jorhat districts of Assam. About 143 plants species were collected which are being used by shan tribe as their supplementary source of food material.