Research involving Human Subjects - Ethical Perspective.

ABSTRACT: Research involving human subjects are important to develop new therapeutics for the betterment of the human race. To take part in such research as volunteers is moral duty of any human. But such experiments should be justifiable and minimal risky for the participants. History of unethical research involving humans led to the development of many guidelines to make such research ethical as well as to gain maximum possible output. Several guidelines have been formulated to ensure research with human participants ethical. All the guidelines emphasize on one thing in particular- informed consent of the human subjects. Other considerations include rational benefit-harm ration, beneficence, justice, adequate research design and approval from proper authorities. All these guidelines aim to prevent any unethical research involving humans against their will.

Scientific Freedom & Limits - Clinical Research Perspective.

ABSTRACT: Being a scientist, especially a clinical research one, is a noble but tough job. Scientific job is different from other jobs in terms of working hour and pressure; they need more freedom in their job & research that also put lots of responsibility on them. Research is funded by public money and it is the responsibility of scientists to gain maximum output from it. Clinical research is very complex and involves the use of animal, microbial as well as human samples and volunteers which make it more prone to ethical scrutiny. Minority of researchers who commit fraudulent use of public money & unethical clinical practice threaten public support for science. Now a day, there is growing concern of public and politicians on the freedom of scientists and unethical scientific practice in clinical trials. The most efficient measures to prevent scientific misconduct are awareness—notably, self-awareness— education and transparency. Most of the developed countries have formulated their own guidelines to ensure proper utilization and ethical clinical research and trials. Bangladesh is still lagging behind in terms of regulation and monitoring of clinical research and trials. This review aims to make related peoples to be aware of the necessity of its own guidelines for clinical research and trials.

Ethics in clinical research.

ABSTRACT: History of unethical clinical research practice date back to a very long time, though the most remarkable unethical clinical research was those by the Nazis during second world war, which eventually shaken the scientific community and gives birth to the first guideline of ethics in clinical research, the Nuremberg Code. Following Nuremberg code, a number of ethical guidelines has been formulated most important of which are the declaration of Helsinski. To make any research involving human subjects or samples ethically acceptable, a number of key features have to be considered by the scientists. These guidelines are internationally accepted and without following these guidelines, no clinical research is acceptable in the world. Though, there are many countries in the world like Bangladesh, which don’t have any ethical guidelines of their own and thus scientists in those countries do not adhere the any ethical guideline while conducting their research. Each country should have their own ethical guidelines and each clinical research institutes should have own ethical review committee to ensure ethical clinical research.

Implications of oxidative stress in pathogenesis of cholestasis.

Cholestasis results from both genetic and acquired conditions causing disordered bile secretion and flow resulting in accumulation of toxic cholephiles in the blood. Prolonged and unrelieved cholestasis leads to liver injury, fibrosis and failure. Recent advances in understanding of the molecular mechanism of cholestasis, including function of biliary transporters and their regulation, have provided significant insights into pathophysiological derangements in cholestasis. Oxidative stress, caused by unchecked and dysregulated accumulation of reactive oxygen species (ROS) has emerged as an important contributor to cholestatic liver injury. Adaptive mechanisms in the liver through participation of redox responsive transcription factors, mainly the Nfr2/Keap1 system, as well as NF-kB and AP-1 are important. Oxidative stress induced actin disorganization with tight-junction impairment and transporter internalization have been observed to occur along with activation of Ca2+ dependent protein kinase C isoforms (cPKCs) in cholestasis related oxidative stress, that plays an important role in secretory failure . Animal models of cholestasis have been developed and inflammation has been found to play a significant role in cholestasis induced liver injury. A complete understanding of the redox sensitive signaling pathways involved in cholestasis is very much essential in order to have a more complete picture for better insight into the selective therapeutic strategies to abrogate ROS mediated harmful pathways, or to enhance the protective ones.

Hepatic fibrosis: can we treat it clinically?

Hepatic fibrosis, a reparative response to different types of liver injury, has emerged as the primary determinant of outcome in advancing chronic liver disease, including cirrhosis. Once considered irreversible, today there is enough clinical as well as laboratory data available for us to be optimistic and expect regression of liver fibrosis in clinical situations, with resultant improvement in outcome. The primary premise of this approach to modify liver fibrosis has been its success in treating the basic pathology underlying persistent liver inflammation and injury, often with the reversal of cirrhosis. However, more focussed anti-fibrotics altering the dynamics of collagen deposition and resorption are undergoing evaluation and will be available shortly. In this changing scenario, there is a need for precise, easy to use endpoints of success/failure of anti-fibrotic therapy. A future scenario may be envisaged as one of a more positive, aggressive approach to treatment of chronic liver disease- treating the cause as well as using anti-fibrotics. This "hit the enemy and repair the hut" approach ushers in a new era from the hitherto barren pessimism in the treatment of chronic liver disease.

Safety and efficacy of an indigenous human recombinant interferon alpha 2b (Shanferon) in patients with chronic hepatitis B.

Interferon treatment is the established option for the treatment of patients with chronic hepatitis B without decompensated liver disease. However, such treatment is expensive. We report here our data of a multi-center, open-label trial of the use of an indigenously produced interferon in the treatment of chronic HBeAg-positive chronic hepatitis B. Adult patients with chronic HBeAg-positive hepatitis B with elevated serum transaminase activity and positive serum HBV DNA test were treated with 5 MU/day of an indigenously produced interferon (Shanferon; Shantha Biotechnics, Hyderabad, India) for 4 months, and were then followed up for 6 months. Of the 39 patients enrolled, 36 completed the treatment and 33 completed the post-treatment follow-up. Of the 33 patients who completed the study, end-of-treatment biochemical and virological responses were observed in 10 (30%) and 5 (15%) respectively. Sustained biochemical and virological responses were observed in 15 (45%) and 7 (21%), patients respectively. Adverse effects led to the discontinuation of treatment in only one patient. Our data suggest that safety and efficacy of the indigenously produced interferon were similar to those previously reported results with interferon from other sources.