Changes of electrocardiogram and hemodynamics in response to dipyridamole: In vivo comparative analyses using anesthetized beagle dogs and microminipigs

Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal. While organic coronary arterial stenosis was not detected in either animal, dogs have well-developed epicardial intracoronary networks unlike microminipigs. Like in humans, dipyridamole did not affect the ST segment of microminipigs, whereas it substantially depressed that in dogs. The results indicate the onset of subendocardial ischemia by dipyridamole in dogs may be partly associated with their well-developed native coronary collateral channels. Microminipigs would be more useful to evaluate the drugs which may affect the coronary circulation in the pre-clinical study than dogs.     

Phase II investigational oral drugs for the treatment of radio/chemotherapy induced oral mucositis

Introduction: Oral mucositis is a significant unmet clinical need for many cancer patients. The biological complexity of mucositis’ pathogenesis provides a number of mechanistic targets suitable as pharmacologic targets. The diversity of targets has stimulated drug development in search of an effective intervention. In this paper, we review a range of agents that are currently being evaluated.

Areas covered: Drugs for management of oral mucositis vary in formulation, route of administration and biological target. Most propose to interrupt the initiation of injury by suppressing activation of the innate immune response or countering oxidative stress, or minimizing downstream inflammatory responses. Overwhelmingly, the population most studied is patients being treated with concomitant chemoradiation for cancers of the head and neck as this is the cohort that most consistently suffers severe mucositis for long periods of time. The Phase 2 pipeline is robust. Preliminary data reported for a number of agents is optimistic. Genomics may be important in interpreting and comparing responses to agents across widely demographically diverse populations.

Expert opinion: Oral mucositis remains a significant toxicity for patients undergoing cancer treatment. Incremental reports of successes have been noted for a number of targeted agents.     

Mechanism of acid production and secretion by osteoclasts]

Osteoclasts are primary cells responsible for bone resorption. The most characteristic feature of osteoclasts is the presence of ruffled borders and clear zones. The resorbing area under the ruffled border of osteoclasts is acidic, which favors dissolution of bone mineral. In bone-resorbing osteoclasts, hydrogen ions are provided by carbonic anhydrase II, which catalyzes the hydration of CO2 to H2CO3. Recently, it has been shown that the proton pump of the vacuolar H(+)-ATPase type exists in the ruffled border membranes of osteoclasts. Secretion of hydrogen ions by osteoclasts generates an equal amount of cytoplasmic base equivalents, principally as HCO3-. Osteoclasts have a chloride/bicarbonate exchanger, which normalizes the intracellular pH when osteoclasts actively resorb bone. In this paper, we review the mechanism of the acid secretion by osteoclasts.     

A Descriptive Analysis of a Community Clinic Providing Hepatitis C Treatment to Poor and Uninsured Patients

This study describes clinical characteristics of poor and uninsured patients living with hepatitis C virus (HCV) who received care from a multidisciplinary HCV clinic, reports treatment completion and cure rates, and estimates the cost of HCV medications provided at no cost to uninsured patients. A retrospective chart review was performed and identified 69 uninsured HCV patients who received medical care at Mercy Health Center, a small non-profit community clinic, between January 2008 and March 2015. Three-fourths of the patients were unemployed, a third had multiple HCV exposures, nearly half acquired HCV due to illicit drug use, and more than half had active psychiatric disorders. Of those who received HCV treatment, 81% completed treatment and 85% were achieved virological cure. The multidisciplinary community clinic provided >?$1.4 million of HCV antivirals at no cost to uninsured patients. Findings suggest a multidisciplinary community clinic comprised of a social worker, pharmacist, gastroenterologist, nurse, nurse practitioner, psychologist, and dietitian can help patients achieve HCV treatment completion and cure rates comparable to traditional physician-led clinics, and successfully manage uninsured and underserved HCV patients—who are often regarded as “difficult-to-treat” patients. Public health social workers and other health professionals are encouraged to advocate for treatment and care of poor and uninsured patients living with HCV in health agencies and health systems, otherwise population-wide reductions in HCV morbidity and mortality will not be realized.