Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg−1 of BPD intravenously 5 min to 180 min before light treatment of 150 J cm−2 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction. © 1999 Cancer Research Campaig

Impact of multiyear La Niña events on the South and East Asian summer monsoon rainfall in observations and CMIP5 models

Impact of multi-year La Niña events on South and East Asian summer monsoon rainfall are examined in the observations and Coupled Model Intercomparison Project Phase 5 (CMIP5) models. The analysis is carried out for the successive two summers, referred to as the first and second years during the period of 1948–2016. Composite analysis suggests that La Niña related sea surface temperature cooling is slightly high in the central and eastern equatorial Pacific during the first year summer. This anomalous cooling associated with La Niña is slightly shifted towards south and south-central Pacific Ocean during the second year. An Atlantic Niño like pattern is evident in the first year unlike the second year. Negative rainfall anomalies are apparent over most of the south Asian region except Bangladesh and Sundarbans, during the first year. Moisture convergence corroborated by low-level circulation to the north of Bangladesh and central India supports the positive rainfall anomalies in the first year. A weak circulation and negative vertically integrated moisture (VIM) anomalies in the rest of the subcontinent are consistent with the negative rainfall anomalies. In addition to these changes, the Atlantic Niño has also been found to be influencing the South Asian rainfall, remotely, during the first year. In the case of the second year, positive rainfall anomalies over the south Asian monsoon region is noted. An anomalous low-level cyclonic circulation over the central Bay of Bengal enhanced the moisture transport into the Indian subcontinent, causing positive rainfall anomalies. Moreover, an anomalous upper level divergence extends from the southeast Indian Ocean, towards the Indian subcontinent, due to La Niña’s response in the second year, which is found to be weak in the first year. This clearly suggests that the enhanced rainfall over the South Asian region is influenced remotely by La Niña forcing as well as local circulation changes during both the years. The East Asian monsoon region reported a tri-pole like structure in the rainfall anomalies, with positive values over southern and central China and negative over parts of Myanmar, Thailand and Cambodia regions and north-east China—North Korea during the first year and vice-versa in the second year. A positive–negative–positive structure in the VIM anomalies is seen in the East Asian region and it supports similar rainfall anomalies during the second year. We have further examined the ability of CMIP5 models in representing multiyear La Niña teleconnections to the south and East Asian summer monsoons. Some models are able to reproduce the South Asian rainfall and circulation anomalies well in the second year, but failed to do so, in the first. The factors responsible for weak teleconnections in the models are discussed in detail