Current pharmaceutical design
-
Perioperative cerebral damage can result in various clinical sequela ranging from minor neurocognitive deficits to catastrophic neurological morbidity with permanent impairment and death. The goal of neuroprotective treatments is to reduce the clinical effects of cerebral damage through two major mechanisms: increased tolerance of neurological tissue to ischemia and changes in intra-cellular responses to energy supply deprivation. In this review, we present the clinical evidence of intravenous anesthetics on perioperative neuroprotection, and we also provide a critical perspective for future studies. ⋯ Current evidence, while inconclusive, suggest that intravenous anesthetics may be both neuroprotective and neurotoxic in the perioperative period. A critical analysis on data recorded from randomized control trials (RCTs) is essential in identifying patients who may benefit or be harmed by a particular anesthetic. RCTs will also contribute to defining methodologies for future studies on the neuroprotective effects of intravenous anesthetics.
-
The recent increase in the prevalence of obesity seems to be responsible for the increase in T2 Diabetes Mellitus (T2DM). At present around 50 % of T2DM patients are obese and this percentage appears set to increase in the near future. Successful management of T2DM in obese patients is a complicated task, as many parameters such as blood pressure, LDL-cholesterol levels have to be adequately controlled along with HbA1c levels. ⋯ However, at present a very small percentage (< 2%) of obese patients with T2DM is treated surgically. The present review focuses on the efficacy and safety of the main bariatric procedures. It also emphasizes the mechanism with which bariatric surgery exerts its therapeutic effect and on the long term results on T2DM remission.
-
Tissue injury secondary to surgical lesion produces profound changes in endocrine-metabolic function and defence mechanisms in the patient (inflammatory, immunological), leading to an increase in catabolism, immunosuppression and postoperative morbidity. The best anaesthetic and surgical technique should be capable of modulating this response, especially in major surgery, where it can be most harmful and increase patient morbidity. Many of the changes that maintain homeostasis are controlled by the hypothalamicpituitary- adrenal axis. ⋯ The aim of this review is to present clinical evidence on perioperative stress modulation with different anesthetics. We also describe a different point of view in immunomodulation with the intraoperative management of haemodynamic responses with inhalational bolus of sevoflurane or with remifentanil intravenous bolus. The effects of sevoflurane used as an inhalational bolus to counteract patients' intraoperative haemodynamic responses modulates the immune response the same than opioid remifentanil.
-
Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. However, the development of new drugs for the treatment and prophylaxis of TB, particularly those truly active against dormant and persistent types of tubercle bacilli, has been slow, although some promising drugs, such as diarylquinoline TMC207, nitroimidazopyran PA-824, nitroimidazo-oxazole Delamanid (OPC-67683), oxazolidinone PNU-100480, ethylene diamine SQ-109, and pyrrole derivative LL3858, are currently under phase 1 to 3 clinical trials. Therefore, novel types of antituberculous drug, which act on unique drug targets in Mycobacterium tuberculosis (MTB) pathogens, particularly drug targets related to the establishment of mycobacterial dormancy in the host's macrophages, are urgently needed. ⋯ I am sincerely grateful to the individuals who contributed to this work. All authors are experts in their fields and they made earnest efforts to perform these in-depth reviews. I thank them all.
-
Leptin hormone plays a vital role in the pathophysiological changes in heart geometry and function. Nonetheless, the precise mechanism(s) triggering leptin-induced cardiomyocyte contractile dysfunction is not well understood. The present study was designed to examine if autophagy plays a role in leptin-induced cardiac contractile anomalies. ⋯ Pharmacological inhibition of reactive oxygen species (ROS) using tempol significantly attenuated leptin-induced autophagosome formation and cardiac contractile anomalies. In addition, genetic deletion of AMPKα2 or pharmacological inhibition of AMPK using compound C abrogated leptin or superoxide induced cardiac contractile dysfunction and autophagosome formation. In summary, our data revealed that leptin impairs cardiac contractile function through a superoxide generation-AMPK activation-and autophagy dependent mechanism.