The role of renin in hypertension : an old dog with new bite / Johannes Marthinus van Rooyen

Foreword: Tigerstedt and Bergman discovered in 1898 the pressure-raising substance from saline rabbit kidney extracts and called the extract renin, however other scientists could not confirm their findings and in 1934, Harry Gold blatt published his results obtained in dog experiments where he clamped one or both renal arteries with a silver clamp. Numerous attempts showed no increases in plasma renin levels in patients with essential hypertension or that renin had any significant physiologic action of its own in humans. Braun-Menendez discovered that renin acted enzymatically on angiotensinogen (plasma protein) to form angiotensin I (inactive) and is further hydrolysed by converting enzyme to form angiotensin II (vasoconstrictor), which increases the blood pressure when it is low. This is the old dog and because renin is not even mentioned in the JNC-VII (US) and the ESH (European) guidelines and when one do a renin profiling on patients/participants and apply the laragh method to individualize the type of hypertension (volume or renin), it is evident that renin plays a large role in the maintenance of normal blood pressure and hypertension. In South African blacks whose hypertension is not under control. this will have a large impact on individualizing specific pathology and treatment and this will give the old dog new bite

Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

<p>Abstract</p> <p>Background</p> <p>Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer.</p> <p>Methods</p> <p>50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio). Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide) were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared.</p> <p>Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was assessed using chi-square test and coefficient of correlation calculated by Pearson correlation coefficient.</p> <p>Results</p> <p>There was a statistically significant correlation observed between clinical, immunohistochemical response (bcl-2/bax ratio) and the drug-induced toxicity.</p> <p>Conclusion</p> <p>Responders also had significant toxicity while non-responders did not show significant toxicity following neoadjuvant chemotherapy. The chemotherapy-induced toxicity was observed to be a cost effective and reliable predictor of response to neo-adjuvant chemotherapy.</p