Enhancing the expression of multi-antigen chimeric TGAGS/BST protein from Toxoplasma gondii in Escherichia coli BL 21 Star during batch cultivation.

Toxoplasmosis, despite advances in science and technology, is a disease that requires attention since there is no vaccine capable of immunizing humans and animals against all isolated types of Toxoplasma gondii. Thus, the use of chimeric proteins, which can contain multiple antigens, is a very promising alternative for the process of obtaining a vaccine and diagnostic test for toxoplasmosis due to the great diversity of antigens presented by T. gondii. In this context, the present study evaluates batch culture strategies in the production of the multi-antigenic chimeric protein TgAGS/BsT from Toxoplasma gondii. Several exploratory cultures were initially carried out to observe the kinetic behavior of E. coli BL21 Star in five different medium compositions without the addition of IPTG (inducer). Cultures of E. coli B21 Star were carried out with 1.0 mM IPTG at different times of initiation of induction (0.5, 1, and 6 h) to evaluate the effects on cell growth, production of the protein of interest, culture pH, and acetic acid formation. The results showed that among the culture media evaluated, 2xTY and TB supplemented with glycerol had the best cell concentration values of 3.42 ± 0.05 g/L and 5.48 ± 0.05 g/L, respectively. In the assays induced by IPTG, a higher expression of TgAGS/BsT protein was observed, with induction beginning within 6 h of culture, with a maximum concentration of protein of interest of 1.82 ± 0.02 g/L for the 2xTY and 2.49 ± 0.03 g/L for the TB medium. In addition, later induction by IPTG provided greater stability of plasmid pET-TgAGS, remaining with values above 90% at the end of culture.

A novel form of dichloroacetate therapy for patients with advanced cancer: a report of 3 cases.

Oral dichloroacetate sodium (DCA) is currently under investigation as a single agent and as an adjuvant for treatment of various cancers. One of the factors limiting its clinical use in a continuous oral regimen is a dose-related, reversible neurotoxicity, including peripheral neuropathy and encephalopathy. The intravenous (IV) route has a number of potential advantages, including (1) pulsed dosing to achieve higher concentrations than feasible with oral use, (2) a longer washout period to reduce the potential for neurotoxicity, and (3) a bypassing of the digestive system, which is particularly significant for advanced-stage cancer patients. Data were available on high-dose IV DCA (up to 100 mg/kg/dose) that have confirmed its safety, both in healthy volunteers and in critically ill patients, allowing the authors to begin off-label treatment of cancer patients. In several of their patients treated with IV DCA, the authors observed clinical, hematological, or radiological responses. This article presents 3 cases with patients who had recurrent cancers and for whom all conventional therapies had failed: (1) a 79-y-old male patient with colon cancer who had liver metastases, (2) a 43-y-old male patient with angiosarcoma who had pancreatic and bone metastases, and (3) a 10-y-old male patient with pancreatic neuroendocrine carcinoma who had liver metastases.

Suicide attempts by jumping and psychotic illness.

BACKGROUND: Several recent studies have reported that serious violence towards self and others is more common in the first episode of psychosis than after treatment. AIM: To estimate the proportion of survivors of suicide attempts during psychotic illness by jumping from a height who had not previously received treatment with antipsychotic medication. METHODS: An audit of the medical records of patients admitted to nine designated trauma centres in New South Wales, Australia, after surviving a jump of more than 3 m. Jumping was defined using routine hospital ascribed International Classification of Diseases (ICD) codes. The height of the jump and all clinical data were extracted from case notes. RESULTS: The files of 160 survivors of jumps of more than 3 m were examined, which included 70 who were diagnosed with a psychotic illness (44%). Thirty-one of the 70 diagnosed with a psychotic illness (44%, 95% confidence interval [CI] 32-56%) had never received treatment for psychosis and hence were in the first episode of psychosis. One in five (19.4%) of all survivors of a suicide attempt by jumping had an undiagnosed and untreated psychosis that was often characterized by frightening delusional beliefs. CONCLUSION: A large proportion of the survivors of suicide attempts by jumping were diagnosed with a psychotic illness, which confirms an association between psychosis and suicide by jumping. Some suicides might not have been linked to psychosis had the patient not survived the suicide attempt, suggesting that the contribution of schizophrenia to suicide mortality might have been underestimated in psychological autopsy studies. The finding that nearly half of the survivors diagnosed to have a psychotic illness had never received treatment with antipsychotic medication indicates a greatly increased risk of suicide by jumping in the first episode of psychosis when compared to the annual risk after treatment.

Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy.

Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard RECIST definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death). A case is presented in which oral DCA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity. Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death, this case highlights a novel use of DCA as a cytostatic agent with a potential to maintain long-term stability of advanced-stage cancer.