Antibody-drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance.

An antibody-drug conjugate (ADC) is an advanced chemotherapeutic option with immense promises in treating many tumor. They are designed to selectively attack and kill neoplastic cells with minimal toxicity to normal tissues. ADCs are complex engineered immunoconjugates that comprise a monoclonal antibody for site-directed delivery and cytotoxic payload for targeted destruction of malignant cells. Therefore, it enables the reduction of off-target toxicities and enhances the therapeutic index of the drug. Hepatocellular carcinoma (HCC) is a solid tumor that shows high heterogeneity of molecular phenotypes and is considered the second most common cause of cancer-related death. Studies show enormous potential for ADCs targeting GPC3 and CD24 and other tumor-associated antigens in HCC with their high, selective expression and show potential outputs in preclinical evaluations. The review mainly highlights the preclinical evaluation of different antigen-targeted ADCs such as MetFab-DOX, Anti-c-Met IgG-OXA, Anti CD 24, ANC-HN-01, G7mab-DOX, hYP7-DCand hYP7-PC, Anti-CD147 ILs-DOX and AC133-vcMMAF against hepatocellular carcinoma and its future relevance.

Treatment outcome of extrapulmonary tuberculosis under Revised National Tuberculosis Control Programme.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) constitutes 15-20% of tuberculosis cases in India. Earlier studies have evaluated treatment outcomes of EPTB with little information on outcomes of individual site of EPTB. AIMS: The objective was to study the outcome of Directly Observed Treatment Short course (DOTS) treatment of EPTB in different organ systems under Revised National Tuberculosis Control Programme. METHODS: Multi-centric retrospectives record review was carried out in three states in India. Data were collected from TB registers and analysed. RESULTS: Of the total 2219 patients studied, there were more males in age group 15-45. The commonest sites of EPTB were lymph node (34.4%) and pleural effusion (25.2%) followed by abdominal (12.8%) and central nervous system (CNS) (9.4%). Lymph node involvement was more common in females (58%) and pleural effusion in males (70%). Overall treatment completion rate was 84% in EPTB patients. Treatment completion was 86% in HIV negative EPTB patients compared to 66% in HIV positive patients. Individually, treatment completion rate observed as follows: lymph node 90.9%, genitourinary 92.6%, bone and joint 86%, pleural effusion 84.7%, abdominal 76% and CNS (tuberculoma and meningitis) 63.7%. The site of EPTB was not recorded in 173 (7.8%) patients. CONCLUSION: Treatment outcome of EPTB was poor in HIV infected patients and those with CNS tuberculosis. More efforts are needed to improve the treatment completion rates in these groups of patients.

Final report on the safety assessment of Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint) Leaf Water.

Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, Mentha Piperita (Peppermint) Leaf Water are obtained from the Mentha piperita plant. The oil is currently used in cosmetic formulations as a fragrance component, but previously had been also described as a denaturant. The extract and leaves are described as biological additives, but only the extract is reported to be used. Peppermint Water is described as a flavoring agent or fragrance component, but is not currently in use. Peppermint Oil is used at a concentration of < or = 3% in rinse-off formulations and < or = 0.2% in leave-on formulations. Peppermint Oil is composed primarily of menthol and menthone. Other possible constituents include pulegone, menthofuran, and limone. Most of the safety test data concern Peppermint Oil. The oil is considered to present the "worst case scenario" because of its many constituents, so data on the oil were considered relevant to the entire group of ingredients. Peppermint Oil was minimally toxic in acute oral studies. Short-term and sub-chronic oral studies reported cystlike lesions in the cerebellum in rats that were given doses of Peppermint Oil containing pulegone, pulegone alone, or large amounts (>200 mg/kg/day) of menthone. Pulegone is also a recognized hepatotoxin. Repeated intradermal dosing with Peppermint Oil produced moderate and severe reactions in rabbits, although Peppermint Oil did not appear to be phototoxic. Peppermint Oil was negative in the Ames test and a mouse lymphoma mutagenesis assay but gave equivocal results in a Chinese hamster fibroblast cell chromosome aberration assay. In a carcinogenicity study of toothpaste and its components, no apparent differences were noted between mice treated with Peppermint Oil and those treated with the toothpaste base. Isolated clinical cases of irritation and/or sensitization to Peppermint Oil and/or its constituents have been reported, but Peppermint Oil (8%) was not a sensitizer when tested using a maximization protocol. It was expected that dermal absorption of Peppermint Oil would be rapid, following that of menthol, a major component, but in no case would be greater than absorption through the gastrointestinal tract. Because of the toxicity of pulegone, the safe concentration of this constituent was limited to < or = 1%. This concentration was achievable both by controlling the time of harvest and processing technique. There is evidence that menthol can enhance penetration of other agents. Formulators were cautioned that this enhanced penetration can affect the use of other ingredients whose safety assessment was based on their lack of absorption. With the limitation that the concentration of pulegone in these ingredients should not exceed 1%, it was concluded that Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Extract, Mentha Piperita (Peppermint) Leaves, Mentha Piperita (Peppermint) Water are safe as used in cosmetic formulations.

Literature review of an underutilized legume: Canavalia gladiata L.

The literature related to the legume commonly known as sword beans (Canavalia gladiata) that belongs to the genus Canavalia which is considered to be an underutilized legume, is reviewed. The legume seeds are considered to be a cheap source of good protein and calories that are easily available. However, even with this knowledge, the utilization of most legumes is apparently low. Sword beans have favorable agronomic features suitable for cultivation in the tropics and a high average yield comparable to that of soybeans. The agroclimatic conditions suitable for cultivation, morphological features, uses, chemical composition and the antinutritional factors of the plant are discussed.

Nutritional evaluation of protein and starch of mature Canavalia gladiata seeds.

Evaluation of true digestibility (TD), biological value (BV) and net protein utilisation (NPU) of diets made with raw and processed seed flour from mature Canavalia gladiata seeds were carried out with male Sprague-Dawley rats. The weight gain of the rats fed with diets containing raw whole seed and raw cotyledon alone were significantly lower (P = 0.05) than that of the group fed with the reference diet. Processing the cotyledons (dry-autoclaved or roasted) significantly (P < or = 0.05) increased the weight gain of the rats when compared to the weight gain of rats fed diets prepared with raw seed flour. NPU of raw (whole seed 13.8; cotyledon 27.6) was significantly lower (P < or = 0.05) than the reference diet (79.5). The NPU of processed samples was also significantly lower (P < or = 0.05) when (dry-autoclaved 25.1; roasted 25.1) compared to the reference diet fed group (79.5). The BV of the processed samples (dry-autoclaved 31.1; roasted 37.7) was significantly lower (P < or = 0.05) than that of raw (53.6) cotyledon. In contrast TD increased (P < or = 0.05) with processing (dry-autoclaved 80.9; roasted 65.9) when compared to raw cotyledon (51.4). In vitro protein digestibility for the raw whole seed and cotyledon was 71.7 and 70.1% respectively. In vitro starch digestibility of raw and processed cotyledon flour samples indicated dry-autoclaved sample to have the highest digestibility.

Alterations in trace element and plasma amino-acid profile in experimental gram-negative septicaemia.

Infection can produce changes in the levels of trace metals such as copper, iron and zinc and several amino acids. These trace metals are involved in many metabolic reactions as well as in the host defence response. In the present study we have induced septicaemia in male Sprague-Dawley rats. The rats were made septic by surgical insertion of a gelatine capsule containing known amounts of E. coli (1.25 x 10(7) bact/ml) and Bacteroides fragiles (2.5 x 10(7) bact/ml) along with sterile rat faeces as an adjuvant (50% vol/vol), and barium sulphate (10% weight/weight) as an irritant into the abdomen. Blood samples were collected at 36, 60 and 72 h to study alterations in the pattern of copper, zinc, calcium and magnesium and plasma amino acids. Liver samples were taken after sacrifice at 72 h for inorganic element analysis. Sepsis produced a significant increase in copper and magnesium and a significant decrease in zinc and calcium levels of plasma. Trace element content of the livers the septic rats did not differ appreciably from control rats. Septic rats also had a lowered concentration of branched chain amino acids. These changes especially those of copper and zinc could be expected to have a role in the progress of the disease. The changes observed in the present study might be caused through the release of Interleukin-I or related substances from the phagocytic cells.